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Not sure what titration is or what you can do with it? Then you are in the right place! In this tutorial, you will find information on titration, including the chemicals that are commonly used and the chemical reactions that make titration work, as well as how titration is performed and some tips to get better results.

Titration is a method commonly used in chemistry to figure out the amount of a chemical in a solution. This chemical is called the titrand. To figure out the amount of titrand in the solution, a known amount of a different chemical is added to the titrand"s solution; this chemical— called the titrant, or titrating solution—reacts with the titrand. By measuring how much of the titrating solution is needed to react with all of the titrand in the solution, you can calculate how much titrand was in the solution. Simply put:

You can watch the video below, made by the Massachusetts Institute of Technology (MIT)"s Department of Chemistry, to see titration in action. Note: This video uses an indicator that turns light pink at the endpoint, but different indicators turn different colors at their endpoints. The next section contains more information about indicators.

There are many different types of indicators used in titration experiments. Which indicator is used depends on the chemistry of the reaction taking place between the titrand and the titrating solution. This titration tutorial will cover two commonly used indicators—starch and phenolphthalein—along with their associated reactions.

Starch is an indicator that reacts with iodine. When there is iodine present, starch reacts with it to create a blue chemical complex. This means the solution turns blue! How is this used in titration? Iodine is included in the titrating solution, and as it is added to the titrand"s solution (which includes the titrand and starch), the titrand reacts with the iodine to turn it into iodide ions (which do not react with the starch). However, as soon as all of the titrand has reacted with the iodine and the endpoint is reached, the addition of any more iodine will finally react with the starch and turn the titrand"s solution blue!

An example of titration using a starch indicator is the titration of vitamin C, which is technically ascorbic acid. Ascorbic acid reacts with iodine to make dehydroascorbic acid and iodide ions. (This reaction is technically an oxidation-reduction reaction, also called a redox reaction for short.) When ascorbic acid and starch are both in a solution, iodine will react with the ascorbic acid. So when titrating ascorbic acid, a titrating solution containing iodine is added to the titrand"s solution, which contains starch (the indicator) and ascorbic acid (the titrand), and when all of the ascorbic acid has reacted with the iodine, any more iodine added will react with the starch and turn the titrand"s solution blue! Figure 1, below, shows a picture of the endpoint of an ascorbic acid titration using starch and iodine. Because there is a known concentration of iodine in the titrating solution, by keeping track of how much solution is added, you can determine how much titrand there was.

Figure 1. The titrand"s solution turns blue-black when the endpoint has been reached in a titration using starch as an indicator (to react with iodine).

Acids, Bases, & the pH Scale.) Specifically, phenolphthalein is colorless when the pH of a solution is acidic or neutral, but when the solution becomes slightly basic, phenolphthalein turns slightly pinkish, and then darker pink as the solution becomes more basic. How is this used in titration? A base is included in the titrating solution, and it is added to the titrand"s solution, which contains an acidic titrand and phenolphthalein. As more base is added to the titrand"s solution, the pH changes, becoming more basic, and the solution changes color. Usually, with this indicator, when the titrand"s solution just starts to turn pink, you have reached the endpoint.

An example of titration usng phenolphthalein is the titration of vinegar, which is technically acetic acid. When titrating acetic acid, a titrating solution containing a base—normally sodium hydroxide—is added to the titrand"s solution, which contains phenolphthalein (the indicator) and acetic acid (the acidic titrand). (The acetic acid reacts with the sodium hydroxide in an acid-base reaction.) When the titrand"s solution becomes basic enough due to the addition of the basic titrating solution, the phenolphthalein turns the titrand"s solution slightly pink. Phenolphthalein is specifically colorless at a neutral or acidic pH, and becomes light pink as the pH becomes more basic (first turning slightly pink around a pH of 8.3). Figure 2, below, shows a picture of the endpoint of an acetic acid titration using phenolphthalein and sodium hydroxide. Because the number of moles of sodium hydroxide used to titrate the acetic acid equals the number of moles of acetic acid in the titrand solution, by keeping track of how much titrating solution is added, you can determine how much titrand there was.

Figure 2. The titrand"s solution turns slightly pink when the endpoint has been reached in a titration using phenolphthalein as an indicator (to show the change in pH).

There are many steps that should be taken to ensure that a titration is successful and that the results produced are accurate. Check out the video of best practices in titration. Here are some key points to follow and keep in mind when doing a titration:

Assembling the titration setup. Figure 3, below, shows what the general titration setup should look like. The buret is held in place by the buret clamp, which is attached to the ring stand. The titrand"s solution should be placed directly under the bottom of the buret, as shown in Figure 4, below. The buret, which can be moved up and down, should be adjusted so that it is just above the opening of the flask containing the titrand"s solution, as shown in Figure 4.

Figure 3. This picture shows a general titration setup. Note that the buret clamp is firmly attached to the ring stand. The buret shown here slides into place between the prongs of the buret clamp. The buret is held firmly in place, but can be moved up and down if needed.

Adding the titrating solution to the titrand"s solution. Using the red stopper at the bottom of the buret, slowly add the titrating solution to the titrand"s solution one drop at a time. It is important to only let the titrating solution be added one drop at a time because the titration reaction can be very sensitive. One drop may be enough to drive the reaction to completion (if it was near completion before). If more than one drop is added at a time, the data may not be as accurate as it could be. After each drop is added, swirl the flask to mix in the titrating solution. When adding the titrating solution, you may see a temporary color change that goes away when you swirl the flask, as shown in Figure 8, below. If this happens, continue adding one drop at a time; you have reached the titration endpoint when there is a more lasting color change throughout the entire titrand"s solution, as shown in

Watching for the endpoint. Add the titrating solution, mixing in one drop at a time by swirling the flask, until a color is seen throughout the solution that lasts for longer than 20 seconds. At this point, you have reached the endpoint and the titration is complete. If you are using starch as an indicator, your endpoint may look similar to Figure 1, whereas if you are using phenolphthalein as an indicator, your endpoint may look similar to Figure 2. Note that different indicators will cause the endpoint to have a different color; you should confirm the expected color of your endpoint before starting the titration. Lastly, it is important to not overshoot the endpoint (by adding too much titrating solution) because this can cause your results to be inaccurate.

Troubleshooting: No color change is seen. There are a number of reasons why a titration may not work. Here are the most common problems that can lead to a titrand"s solution not changing colors:

Using incorrect concentrations. If you are performing an ascorbic acid titration and the standard solution is too concentrated, or your titrating solution is too diluted, or your indicator solution is not the correct concentration, it may require more than 50 mL of iodine solution to titrate the sample. Note: When doing an ascorbic acid titration, the most common problem here is an overly diluted iodine solution; sometimes the Lugol"s iodine solution sold in stores is already diluted and you do not need to dilute it more.

In the example titration using phenolphthalein in the titration of acetic acid, the unknown amount of acetic acid (the titrand) can again be determined by setting up a proportion with the known amount of sodium hydroxide (the titrating solution). Specifically, the number of moles of sodium hydroxide used to titrate the acetic acid equals the number of moles of acetic acid in the titrand"s solution. For example, if you added 12.5 mL (0.0125 liters [L]) of a 0.1 molar (M, which is moles/L) sodium hydroxide to titrate the acetic acid, the number of moles of both sodium hydroxide and acetic acid would be 0.0125 L x 0.1 moles/L = 0.00125 moles. You could divide by the amount of the sample (in liters) to determine the molar concentration of the acetic acid. For example, if your sample volume was 1.5 mL (0.0015 L), it would have a molarity of 0.00125 moles / 0.0015 L = 0.833 M.

Tabacco, S. and Siddiqui, A. (2003). The Digital Lab Techniques Manual: Titration. Massachusetts Institute of Technology (MIT). Department of Chemistry. Retrieved November 8, 2013.

A complete understanding of a chemical concept is dependent upon a student"s ability to understand the microscopic or particulate nature of the phenomenon and integrate the microscopic, symbolic, and macroscopic representations of the phenomenon. Acid-base chemistry is a general chemistry topic requiring students to understand the topics of chemical reactions, solutions, and equilibrium presented earlier in the course. In this study, twenty-five student volunteers from a second semester general chemistry course completed two interviews. The first interview was completed prior to any classroom instruction on acids and bases. The second interview took place after classroom instruction, a prelab activity consisting of a titration calculation worksheet, a titration computer simulation, or a microscopic level animation of a titration, and two microcomputer-based laboratory (MBL) titration experiments. During the interviews, participants were asked to define and describe acid-base concepts and in the second interview they also drew the microscopic representations of four stages in an acid-base titration. An analysis of the data showed that participants had integrated the three representations of an acid-base titration to varying degrees. While some participants showed complete understanding of acids, bases, titrations, and solution chemistry, other participants showed several alternative conceptions concerning strong acid and base dissociation, the formation of titration products, and the dissociation of soluble salts. Before instruction, participants" definitions of acid, base, and pH were brief and consisted of descriptive terms. After instruction, the definitions were more scientific and reflected the definitions presented during classroom instruction.

In the triage of hits from a high-throughput screening campaign or during the optimization of a lead compound, it is relatively routine to test compounds at multiple concentrations to determine potency and maximal effect. Additional follow-up experiments, such as agonist shift, can be quite valuable in ascertaining compound mechanism of action (MOA). However, these experiments require cross-titration of a test compound with the activating ligand of the receptor requiring 100-200 data points, severely limiting the number tested in MOA assays in a screening triage. We describe a process to enhance the throughput of such cross-titration experiments through the integration of Hewlett Packard"s D300 digital dispenser onto one of our robotics platforms to enable on-the-fly cross-titration of compounds in a 1536-well plate format. The process handles all the compound management and data tracking, as well as the biological assay. The process relies heavily on in-house-built software and hardware, and uses our proprietary control software for the platform. Using this system, we were able to automate the cross-titration of compounds for both positive and negative allosteric modulators of two different G protein-coupled receptors (GPCRs) using two distinct assay detection formats, IP1 and Ca 2+ detection, on nearly 100 compounds for each target.

Ascorbic acid is suggested as the weighable compound for the standardization of iodine solutions in an analytical experiment in general chemistry. The experiment involves an iodometric titration in which iodine reacts with ascorbic acid, oxidizing it to dehydroascorbic acid. The redox titration endpoint is determined by the first iodine excess that is complexed with starch, giving a deep blue-violet color. The results of the titration of iodine solution using ascorbic acid as a calibration standard were compared with the results acquired by the classic method using a standardized solution of sodium thiosulfate. The standardization of the iodine solution using ascorbic acid was accurate and precise, with the advantages of saving time and avoiding mistakes due to solution preparation. The colorless ascorbic acid solution gives a very clear and sharp titration end point with starch. It was shown by thermogravimetric analysis that ascorbic acid can be dried at 393 K for 2 h without decomposition. This experiment allows general chemistry students to perform an iodometric titration during a single laboratory period, determining with precision the content of vitamin C in pharmaceutical formulations.

The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper.

Reviews the requirements of the National Titration Competition and describes how a team in a local competition used the technique. Compares microscale titration to conventional titration. Outlines the benefits of employing microscale techniques. (DDR)

Describes a spectrophotometric titration experiment which uses a manual titration spectrophotometer and manually operated buret, rather than special instrumentation. Identifies the equipment, materials, and procedures needed for the completion of the experiment. Recommends the use of this experiment in introductory quantitative analysis…

Presents an experiment in thermometric titration used in an analytic chemistry-chemical instrumentation course, consisting of two titrations, one a mixture of calcium and magnesium, the other of calcium, magnesium, and barium ions. Provides equipment and solutions list/specifications, graphs, and discussion of results. (JM)

A new method to convert the potential of an ion-selective electrode to concentration or activity in potentiometric titration is proposed. The advantage of this method is that the electrode standard potential and the slope of the calibration curve do not have to be known. Instead two activities on the titration curve have to be estimated e.g. the starting activity before the titration begins and the activity at the end of the titration in the presence of large excess of titrant. This new method is beneficial when the analyte is in a complexed matrix or in a harsh environment which affects the properties of the electrode and the traditional calibration procedure with standard solutions cannot be used. The new method was implemented both in a method of linearization based on the Grans"s plot and in determination of the stability constant of a complex and the concentration of the complexing ligand in the sample. The new method gave accurate results when using titrations data from experiments with samples of known composition and with real industrial harsh black liquor sample. A complexometric titration model was also developed. Copyright © 2015 Elsevier B.V. All rights reserved.

In this paper, we developed a novel method of acid-base titration, viz. the electromigration acid-base titration (EABT), via a moving neutralization boundary (MNR). With HCl and NaOH as the model strong acid and base, respectively, we conducted the experiments on the EABT via the method of moving neutralization boundary for the first time. The experiments revealed that (i) the concentration of agarose gel, the voltage used and the content of background electrolyte (KCl) had evident influence on the boundary movement; (ii) the movement length was a function of the running time under the constant acid and base concentrations; and (iii) there was a good linearity between the length and natural logarithmic concentration of HCl under the optimized conditions, and the linearity could be used to detect the concentration of acid. The experiments further manifested that (i) the RSD values of intra-day and inter-day runs were less than 1.59 and 3.76%, respectively, indicating similar precision and stability in capillary electrophoresis or HPLC; (ii) the indicators with different pK(a) values had no obvious effect on EABT, distinguishing strong influence on the judgment of equivalence-point titration in the classic one; and (iii) the constant equivalence-point titration always existed in the EABT, rather than the classic volumetric analysis. Additionally, the EABT could be put to good use for the determination of actual acid concentrations. The experimental results achieved herein showed a new general guidance for the development of classic volumetric analysis and element (e.g. nitrogen) content analysis in protein chemistry. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Significant attention is paid to the proper technique for reading a meniscus. Video shows meniscus-viewing techniques for colorless and dark liquids and the consequences of not reading a meniscus at eye level. Lessons are provided on approaching the end point, focusing on end point colors produced via different commonly used indicators. The concept of a titration curve is illustrated by means of a pH meter. Carefully recorded images of the entire range of meniscus values in a buret, pipet, and graduated cylinder are included so that you can show your students, in lecture or pre-lab discussion, any meniscus and discuss how to read the buret properly. These buret meniscus values are very carefully recorded at the rate of one video frame per hundredth of a milliliter, so that an image showing any given meniscus value can be obtained. These images can be easily incorporated into a computer-based multimedia environment for testing or meniscus-reading exercises. Two of the authors have used this technique and found the exercise to be very well received by their students. Video on side two shows nearly 100 "bloopers", demonstrating both the right way and wrong ways to do tasks associated with titration. This material can be used in a variety of situations: to show students the correct way to do something; to test students by asking them "What is this person doing wrong?"; or to develop multimedia, computer-based lessons. The contents of Titration Techniques are listed below: Side 1 Titration: what it is. A simple titration; Acid-base titration animation; A brief redox titration; Redox titration animation; A complete acid-base titration. Titration techniques. Hand technique variations; Stopcock; Using a buret to measure liquid volumes; Wait before reading meniscus; Dirty and clean burets; Read meniscus at eye level (see Fig. 1); Meniscus viewing techniques--light colored liquids; Meniscus viewing techniques--dark liquids; Using a magnetic stirrer; Rough titration

Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

Coulometric titrations involve the quantification of analyte by measurements of current and time. In most coulometric titrations, the anode and cathode are placed in isolated cells that are connected by a salt bridge. By contrast, the experiments described here involve coulometric titrations (of acidic protons in solution) using a silver anode and…

Presents an experiment that uses a unique acid-base indicator--the odor of raw onion--to indicate the end point of the titration of sodium hydroxide with hydrochloric acid. Allows the student to detect the completion of the neutralization reaction by olfaction rather than sight. (JRH)

A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

Direct thermometric titration of sulphate with a solution of barium perchlorate is proposed. The stoichiometry of the titration is shown to be critically dependent on the concentration of ethanol in the titration medium. The titration is rapid and suffers from only a few interferences.

Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

It has been experimentally shown that ejection of double-stranded DNA from phage is driven by internal pressure reaching tens of atmospheres. This internal pressure is partially responsible for delivery of DNA into the host cell. While several theoretical models and simulations nicely describe the experimental data of internal forces either resisting active packaging or equivalently favoring spontaneous ejection, there are no direct energy measurements available that would help to verify how quantitative these theories are. We performed direct measurements of the enthalpy responsible for DNA ejection from phage λ, using Isothermal Titration Calorimetry. The phage capsids were ``opened"" in vitro by titrating λ into a solution with LamB receptor and the enthalpy of DNA ejection process was measured. In his way, enthalpy stored in λ was determined as a function of packaged DNA length comparing wild-type phage λ (48.5 kb) with a shorter λ-DNA length mutant (37.7 kb). The temperature dependence of the ejection enthalpy was also investigated. The values obtained were in good agreement with existing models and provide a better understanding of ds- DNA packaging and release mechanisms in motor-packaged viruses (e.g., tailed bacteriophages, Herpes Simplex, and adenoviruses).

1. The usefulness of the radiomicrometer in titration work has been pointed out. The authors suggest that light titration may also be used where a reaction mixture changes its absorption in the (near) infra-red. 2. The applicability of this method to the starch-iodine reaction has been demonstrated. PMID:19872266

The determination of sulfate concentration in water by indirect EDTA titration is an instructive experiment that is easily implemented in an analytical chemistry laboratory course. A water sample is treated with excess barium chloride to precipitate sulfate ions as BaSO[subscript 4](s). The unprecipitated barium ions are then titrated with EDTA.…

Sorption reactions on natural or synthetic materials that can attenuate the migration of pollutants in the geosphere could be affected by temperature variations. Nevertheless, most of the theoretical models describing sorption reactions are at 25 degrees C. To check these models at different temperatures, experimental data such as the enthalpies of sorption are thus required. Highly sensitive microcalorimeters can now be used to determine the heat effects accompanying the sorption of radionuclides on oxide-water interfaces, but enthalpies of sorption cannot be extracted from microcalorimetric data without a clear knowledge of the thermodynamics of protonation and deprotonation of the oxide surface. However, the values reported in the literature show large discrepancies and one must conclude that, amazingly, this fundamental problem of proton binding is not yet resolved. We have thus undertaken to measure by titration microcalorimetry the heat effects accompanying proton exchange at the alumina-water interface at 25 degrees C. Based on (i) the surface sites speciation provided by a surface complexation model (built from acid-base titrations at 25 degrees C) and (ii) results of the microcalorimetric experiments, calculations have been made to extract the enthalpic variations associated respectively to first and second deprotonation of the alumina surface. Values obtained are deltaH1 = 80+/-10 kJ mol(-1) and deltaH2 = 5+/-3 kJ mol(-1). In a second step, these enthalpy values were used to calculate the alumina surface acidity constants at 50 degrees C via the van"t Hoff equation. Then a theoretical titration curve at 50 degrees C was calculated and compared to the experimental alumina surface titration curve. Good agreement between the predicted acid-base titration curve and the experimental one was observed.

The aims of the present study were twofold. We sought to compare two methods of titrating the level of continuous positive airway pressure (CPAP) - auto-adjusting titration and titration using a predictive equation - with full-night manual titration used as the benchmark. We also investigated the reliability of the two methods in patients with obstructive sleep apnea syndrome (OSAS). Twenty consecutive adult patients with OSAS who had successful, full-night manual and auto-adjusting CPAP titration participated in this study. The titration pressure level was calculated with a previously developed predictive equation based on body mass index and apnea-hypopnea index. The mean titration pressure levels obtained with the manual, auto-adjusting, and predictive equation methods were 9.0 +/- 3.6, 9.4 +/- 3.0, and 8.1 +/- 1.6 cm H2O,respectively. There was a significant difference in the concordance within the range of +/- 2 cm H2O (p = 0.019) between both the auto-adjusting titration and the titration using the predictive equation compared to the full-night manual titration. However, there was no significant difference in the concordance within the range of +/- 1 cm H2O (p > 0.999). When compared to full-night manual titration as the standard method, auto-adjusting titration appears to be more reliable than using a predictive equation for determining the optimal CPAP level in patients with OSAS.

The feasibility of implementing tracer-monitored titrations in a flow system is demonstrated. A dye tracer is used to estimate the instant sample and titrant volumetric fractions without the need for volume, mass or peak width measurements. The approach was applied to spectrophotometric flow titrations involving variations of sample and titrant flow-rates (i.e. triangle programmed technique) or concentration gradients established along the sample zone (i.e. flow injection system). Both strategies required simultaneous monitoring of two absorbing species, namely the titration indicator and the dye tracer. Mixing conditions were improved by placing a chamber with mechanical stirring in the analytical path aiming at to minimize diffusional effects. Unlike most of flow-based titrations, the innovation is considered as a true titration, as it does not require a calibration curve thus complying with IUPAC definition. As an application, acidity evaluation in vinegars involving titration with sodium hydroxide was selected. Phenolphthalein and brilliant blue FCF were used as indicator and dye tracer, respectively. Effects of sample volume, titrand/titrant concentrations and flow rates were investigated aiming at improved accuracy and precision. Results were reliable and in agreement with those obtained by a reference titration procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhalant allergy, or "atopy" as it is now termed, is the best understood form of allergy today. In some circles, it is the only recognized form of allergy. While an overall picture of its effects on the body and a reasonable approach to its treatment now exist, many problems remain to be solved and much improvement in its treatment will probably occur within the next several years. Many new approaches to treatment of aeroallergens are now available; however, all are compared with the skin test, which is and has been the baseline for testing and treatment. Endpoint titration provides a quantitative means for undertaking treatment of aeroallergen sensitivity. In no other way does it differ from the forms of skin testing that have been widely used for generations. The practitioners of endpoint titration feel that this difference is highly significant in simplifying, validating, and shortening the necessary period of therapy. While the concept of endpoint titration is not difficult, it is by definition a quantitative form of testing and requires a degree of expertise in performing it correctly. While a good understanding of the method may be gained from the literature, adequate hands-on experience should be obtained by any physician prior to instituting the technique as a treatment modality. Once mastered, it becomes a reliable baseline for all forms of inhalant allergy care.

We compared the ability of two theoretical methods of pH-dependent conformational calculations to reproduce experimental potentiometric titration curves of two models of peptides: Ac-K5-NHMe in 95% methanol (MeOH)/5% water mixture and Ac-XX(A)7OO-NH2 (XAO) (where X is diaminobutyric acid, A is alanine, and O is ornithine) in water, methanol (MeOH), and dimethyl sulfoxide (DMSO), respectively. The titration curve of the former was taken from the literature, and the curve of the latter was determined in this work. The first theoretical method involves a conformational search using the electrostatically driven Monte Carlo (EDMC) method with a low-cost energy function (ECEPP/3 plus the SRFOPT surface-solvation model, assumming that all titratable groups are uncharged) and subsequent reevaluation of the free energy at a given pH with the Poisson-Boltzmann equation, considering variable protonation states. In the second procedure, molecular dynamics (MD) simulations are run with the AMBER force field and the generalized Born model of electrostatic solvation, and the protonation states are sampled during constant-pH MD runs. In all three solvents, the first pKa of XAO is strongly downshifted compared to the value for the reference compounds (ethylamine and propylamine, respectively); the water and methanol curves have one, and the DMSO curve has two jumps characteristic of remarkable differences in the dissociation constants of acidic groups. The predicted titration curves of Ac-K5-NHMe are in good agreement with the experimental ones; better agreement is achieved with the MD-based method. The titration curves of XAO in methanol and DMSO, calculated using the MD-based approach, trace the shape of the experimental curves, reproducing the pH jump, while those calculated with the EDMC-based approach and the titration curve in water calculated using the MD-based approach have smooth shapes characteristic of the titration of weak multifunctional acids with small differences

Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQ(V) = δq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal-ligand pairs studied.

Nanoparticles (NP), when exposed to biological fluids, are coated by specific proteins that form the so-called protein corona. While some adsorbing proteins exchange with the surroundings on a short time scale, described as a "dynamic" corona, others with higher affinity and long-lived interaction with the NP surface form a "hard" corona (HC), which is believed to mediate NP interaction with cellular machineries. In-depth NP protein corona characterization is therefore a necessary step in understanding the relationship between surface layer structure and biological outcomes. In the present work, we evaluate the protein composition and stability over time and we systematically challenge the formed complexes with surfactants. Each challenge is characterized through different physicochemical measurements (dynamic light scattering, ζ-potential, and differential centrifugal sedimentation) alongside proteomic evaluation in titration type experiments (surfactant titration). 100 nm silicon oxide (Si) and 100 nm carboxylated polystyrene (PS-COOH) NPs cloaked by human plasma HC were titrated with 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS, zwitterionic), Triton X-100 (nonionic), sodium dodecyl sulfate (SDS, anionic), and dodecyltrimethylammonium bromide (DTAB, cationic) surfactants. Composition and density of HC together with size and ζ-potential of NP-HC complexes were tracked at each step after surfactant titration. Results on Si NP-HC complexes showed that SDS removes most of the HC, while DTAB induces NP agglomeration. Analogous results were obtained for PS NP-HC complexes. Interestingly, CHAPS and Triton X-100, thanks to similar surface binding preferences, enable selective extraction of apolipoprotein AI (ApoAI) from Si NP hard coronas, leaving unaltered the dispersion physicochemical properties. These findings indicate that surfactant titration can enable the study of NP-HC stability through surfactant variation and also selective separation

This experiment describes a simple protocol for teaching acid-base titrations using potentiometry, conductivity, and/or photometry to determine end points without an added indicator. The chosen example examines the titratable acidity of a red wine with NaOH. Wines contain anthocyanins, the colors of which change with pH. Importantly, at the…

In this study, Na(+) uptake and acid-base balance in the euryhaline pupfish Cyprinodon variegatus variegatus were characterized when fish were exposed to pH 4.5 freshwater (7mM Na(+)). Similar to the related cyprinodont, Fundulus heteroclitus, Na(+) uptake was significantly inhibited when exposed to low pH water. However, it initially appeared that C. v. variegatus increased apparent net acid excretion at low pH relative to circumneutral pH. This result is opposite to previous observations for F. heteroclitus under similar conditions where fish were observed to switch from apparent net H(+) excretion at circumneutral pH to apparent net H(+) uptake at low pH. Further investigation revealed disparate observations between these studies were the result of using double endpoint titrations to measure titratable alkalinity fluxes in the current study, while the earlier study utilized single endpoint titrations to measure these fluxes (i.e.,. Cyprinodon acid-base transport is qualitatively similar to Fundulus when characterized using single endpoint titrations). This led to a comparative investigation of these two methods. We hypothesized that either the single endpoint methodology was being influenced by a change in the buffer capacity of the water (e.g., mucus being released by the fish) at low pH, or the double endpoint methodology was not properly accounting for ammonia flux by the fish. A series of follow-up experiments indicated that buffer capacity of the water did not change significantly, that excretion of protein (a surrogate for mucus) was actually reduced at low pH, and that the double endpoint methodology does not properly account for NH(3) excretion by fish under low pH conditions. As a result, it overestimates net H(+) excretion during low pH exposure. After applying the maximum possible correction for this error (i.e., assuming that all ammonia is excreted as NH(3)), the double endpoint methodology indicates that net H(+) transport was reduced to

Discusses ways in which datalogging equipment can enable titration curves to be measured accurately and how computing power can be used to predict the shape of curves. Highlights include sources of error, use of spreadsheets to generate titration curves, titration of a weak acid with a strong alkali, dibasic acids, weak acid and weak base, and…

Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration. A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting. The final model had five variables: warfarin indication, insurance status, number of doctor"s visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction. Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Potentiometric titrations are widely taught in first-year undergraduate courses to connect electrochemistry, stoichiometry, and equilibria and to reinforce acid-base titrations. Students perform a potentiometric titration that is then analyzed to determine analyte concentrations and the solubility product constant of the solid species.

Current Isothermal Titration Calorimetry (ITC) data in the literature have relatively high errors in the measured enthalpies of protein-ligand binding reactions. There is a need for universal validation standards for titration calorimeters. Several inorganic salt co-precipitation and buffer protonation reactions have been suggested as possible enthalpy standards. The performances of several commercial calorimeters, including the VP-ITC, ITC200, and Nano ITC-III, were validated using these suggested standard reactions. PMID:19582227

To improve up-titration of medications to target dose in heart failure patients by improving communication from hospital to primary care. This quality improvement project was undertaken within three heart failure disease management (HFDM) services in Queensland, Australia. A structured medication plan was collaboratively designed and implemented in an iterative manner, using methods including awareness raising and education, audit and feedback, integration into existing work practice, and incentive payments. Evaluation was undertaken using sequential audits, and included process measures (use of the titration plan, assignment of responsibility) and outcome measures (proportion of patients achieving target dose) in HFDM service patients with reduced left ventricular ejection fraction. Comparison of the three patient cohorts (pre-intervention cohort A n=96, intervention cohort B n=95, intervention cohort C n=89) showed increase use of the titration plan, a shift to greater primary care responsibility for titration, and an increase in the proportion of patients achieving target doses of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) (A 37% vs B 48% vs C 55%, p=0.051) and beta-blockers (A 38% vs B 33% vs C 51%, p=0.045). Combining all three cohorts, patients not on target doses when discharged from hospital were more likely to achieve target doses of ACEI/ARB (p<0.0001) and beta blockers (p<0.0001) within six months if they received a medication titration plan. A medication titration plan was successfully implemented in three HFDM services and improved transitional communication and achievement of target doses of evidence-based therapies within six months of hospital discharge. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reviews the advantages of computer simulated environments for experiments, referring in particular to acid-base titrations. Includes pre-lab instructions and a sample computer printout of a student"s use of an acid-base simulation. Ten references. (PR)

Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

A new titration system for studying protein-ligand interactions has been developed. In this system, the sample solution is circulated in the route formed by an access path in a split superconducting magnet to maintain a constant protein concentration during the titration experiments. A concentration-control procedure for the ligand/protein ratio is devised, and the ligand/protein ratio is well controlled by this apparatus.

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

An experiment is described to introduce students to an important class of solid-state reactions while reinforcing concepts of titration by using a pH meter and a powder X-ray diffractometer. The experiment was successful in teaching students the abstract concepts of solid-state structure and diffraction by applying the diffraction concepts learned…

The potentiometric titrations of Zn2+, Cu2+ and 12 Ln3+ metal ions were obtained in ethanol to determine the titration constants (defined as the at which the [-OEt]/[Mx+]t ratios are 0.5, 1.5, and 2.5) and in two cases (La3+ and Zn2+) a complete speciation diagram. Several simple monobasic acids and aminium ions were also titrated to test the validity of experimental titration measurements and to establish new constants in this medium that will be useful for the preparation of buffers and standard solutions. The dependence of the titration constants on the concentration and type of metal ion and specific counterion effects is discussed. In selected cases, the titration profiles were analyzed using a commercially available fitting program to obtain information about the species present in solution, including La3+ for which a dimer model is proposed. The fitting provides the microscopic values for deprotonation of one to four metal-bound ethanol molecules. Kinetics for the La3+-catalyzed ethanolysis of paraoxon as a function of are presented and analyzed in terms of La3+ speciation as determined by the analysis of potentiometric titration curves. The stability constants for the formation of Zn2+ and Cu2+ complexes with 1,5,9-triazacyclododecane as determined by potentiometric titration are presented.

Study Objectives: Depression is a risk factor for medication non-compliance. We aimed to identify if depression is associated with poorer adherence during home-based autotitrating continuous positive airway pressure (autoPAP) titration. Design: Mixed retrospective-observational study. Setting: Academic center. Participants: Two-hundred forty continuous positive airway pressure-naïve obstructive sleep apnea (OSA) patients. Measurements: Patients underwent approximately 1 week of home-based autoPAP titration with adherence data downloaded from the device. Electronic hospital records were reviewed in a consecutive manner for inclusion. Three areas of potential predictors were examined: (i) demographics and clinical factors, (ii) disease severity, and (iii) device-related variables. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Scores on the subscales were categorized as normal or clinical diagnoses of depression (≥ 8) and anxiety (≥ 11). The primary outcome variable was the mean hours of autoPAP used per night. Results: Patients were diagnosed with OSA by either attended polysomnography (n = 73, AHI 25.5[15.1-41.5]) or unattended home oximetry (n = 167, ODI3 34.0[22.4-57.4]) and had home-based autoPAP titration over 6.2 ± 1.2 nights. Mean autoPAP use was 4.5 ± 2.4 hours per night. Multiple linear regression analysis revealed that depression and lower 95th percentile pressures significantly predicted lesser hours of autoPAP use (R2 = 0.19, p < 0.001). Significantly milder OSA in those requiring lower pressures may have confounded the relationship between 95th percentile pressure and autoPAP use. Conclusion: Depression was independently associated with poorer adherence during home-based autoPAP titration. Depression may be a potential target for clinicians and future research aimed at enhancing adherence to autoPAP therapy. Citation: Law M; Naughton M; Ho S; Roebuck T; Dabscheck E. Depression may reduce adherence

Monosegmented flow analysis (MSFA) has been used as a flow-batch system to produce a simple, robust, and mechanized titrator that enables true titrations to be performed without the use of standards. This paper also introduces the use of coulometry with monosegmented titration by proposing a versatile flow cell. Coulometric generation of the titrand is attractive for titrations performed in monosegmented systems, because the reagent can be added without increasing the volume of sample injected. Also, biamperomeric and potentiometric detection of titration end-points can increase the versatility of the monosegmented titrator. The cell integrates coulometric generation of the titrand with detection of end-point by potentiometry or biamperometry. The resulting titrator is a flow-batch system in which the liquid monosegment, constrained by the interfaces of the gaseous carrier stream, plays the role of a sample of known volume to be titrated. The system has been used for determination of ascorbic acid, by coulometric generation of I2 with biamperometric detection, and for determination of Fe(II), by coulometric generation of Ce(IV) with potentiometric detection of the end-point, both in feed supplements.

This study aimed to evaluate the demographics of spasmodic dysphonia in the Indian population and to analyse the optimum dose titration of botulinum toxin type A in this group. A comparative analysis with international studies was also performed. The study involved a retrospective analysis and audit of botulinum toxin type A dose titration in spasmodic dysphonia patients who visited our voice clinic between January 2005 and January 2012. The average total therapeutic dose required for patients with adductor spasmodic dysphonia was 4.2 U per patient per vocal fold (total 8.4 U per patient), and for patients with abductor spasmodic dysphonia, it was 4.6 U per patient. Our audit revealed that 80 per cent of the spasmodic dysphonia patients were male, which contrasts dramatically with international studies, wherein around 80 per cent of spasmodic dysphonia patients were female. Our study also revealed a higher dose titration of botulinum toxin for the Indian spasmodic dysphonia population in both adductor and abductor spasmodic dysphonia cases.

Results from a high-resolution deoxyribonuclease I (DNase I) footprinting titration procedure are described that identify preferred daunomycin binding sites within the 160 bp tyr T DNA fragment. We have obtained single-bond resolution at 65 of the 160 potential binding sites within the tyr T fragment and have examined the effect of 0-3.0 microM total daunomycin concentration on the susceptibility of these sites toward digestion by DNase I. Four types of behavior are observed: (i) protection from DNase I cleavage; (ii) protection, but only after reaching a critical total daunomycin concentration; (iii) enhanced cleavage; (iv) no effect of added drug. Ten sites were identified as the most strongly protected on the basis of the magnitude of the reduction of their digestion product band areas in the presence of daunomycin. These were identified as the preferred daunomycin binding sites. Seven of these 10 sites are found at the end of the triplet sequences 5"ATGC and 5"ATCG, where the notation AT indicates that either A or T may occupy the position. The remaining three strongly protected sites are found at the ends of the triplet sequence 5"ATCAT. Of the preferred daunomycin binding sites we identify in this study, the sequence 5"ATCG is consistent with the specificity predicted by the theoretical studies of Chen et al. [Chen, K.-X., Gresh, N., & Pullman, B. (1985) J. Biomol. Struct. Dyn. 3, 445-466] and is the very sequence to which daunomycin is observed to be bound in two recent X-ray crystallographic studies. Solution studies, theoretical studies, and crystallographic studies have thus converged to provide a consistent and coherent picture of the sequence preference of this important anticancer antibiotic.

A three-hour laboratory experiment, designed for an advanced undergraduate course in instrumental analysis that illustrates the application of the gradient chamber flow-injection titration (GCFIT) method with spectrophotometric detection to determine acidity constants is presented. The procedure involves the use of an acid-base indicator to obtain…

A comprehensive study on the binding of phenazinium dyes viz. janus green B, indoine blue, safranine O and phenosafranine with double stranded poly(A) using various spectroscopic and calorimetric techniques is presented. A higher binding of janus green B and indoine blue over safranine O and phenosafranine to poly(A) was observed from all experiments. Intercalative mode of binding of the dyes was inferred from fluorescence polarization anisotropy, iodide quenching and viscosity experiments. Circular dichroism study revealed significant perturbation of the secondary structure of poly(A) on binding of these dyes. Results from isothermal titration calorimetry experiments suggested that the binding was predominantly entropy driven with a minor contribution of enthalpy to the standard molar Gibbs energy. The results presented here may open new opportunities in the application of these dyes as RNA targeted therapeutic agents.

Quantification of the many constituents that make up our food, whether they are desirable (vitamins, antioxidants, nutrients) or undesirable (pesticides, toxins), is one of the most practical applications of chemistry. In this study, kombucha, a popular fermented tea beverage, was analyzed using acid-base titration and high-performance liquid…

An easy analytical method for determination of the charge density of polyelectrolytes, including polysaccharides and other biopolymers, is presented. The basic principles of conductometric titration, which is used in the pulp and paper industry as well as in colloid and interface science, were adapted to quantify the charge densities of a…

Moving reaction boundary titration (MRBT) has a potential application to immunoassay and protein content analysis with high selectivity. However, air bubbles often impair the accuracy of MRBT, and the leakage of electrolyte greatly decreases the safety and convenience of electrophoretic titration. Addressing these two issues a reliable MRBT device with modified electrolyte chamber of protein titration was designed. Multiphysics computer simulation was conducted for optimization according to two-phase flow. The single chamber was made of two perpendicular cylinders with different diameters. After placing electrophoretic tube, the resident air in the junction next to the gel could be eliminated by a simple fast electrolyte flow. Removing the electrophoretic tube automatically prevented electrolyte leakage at the junction due to the gravity-induced negative pressure within the chamber. Moreover, the numerical simulation and experiments showed that the improved MRBT device has following advantages: (i) easy and rapid setup of electrophoretic tube within 20 s; (ii) simple and quick bubble dissipates from the chamber of titration within 2 s; (iii) no electrolyte leakage from the two chambers: and (iv) accurate protein titration and safe instrumental operation. The developed technique and apparatus greatly improves the performance of the previous MRBT device, and providing a new route toward practical application. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Several recent studies have made use of continuous acid-base titration data to describe the surface chemistry of bacterial cells as a basis for accurately modelling metal adsorption to bacteria and other biomaterials of potential industrial importance. These studies do not share a common protocol; rather they titrate in different pH ranges and they use different stability criteria to define equilibration time during titration. In the present study we investigate the kinetics of bacterial titrations and test the effect they have on the derivation of functional group concentrations and acidity constants. We titrated suspensions of Pantoea agglomerans by varying the equilibration time between successive titrant additions until stability of 0.1 or 0.001 mV s(-1) was attained. We show that under longer equilibration times, titration results are less reproducible and suspensions exhibit marginally higher buffering. Fluorescence images suggest that cell lysis is not responsible for these effects. Rather, high DOC values and titration reversibility hysterisis after long equilibration times suggest that variability in buffering is due to the presence of bacterial exudates, as demonstrated by titrating supernatants separated from suspensions of different equilibration times. It is recommended that an optimal equilibration time is always determined with variable stability control and preliminary reversibility titration experiments. Copyright © 2011 Elsevier Inc. All rights reserved.

Demonstrates how the symmetry properties of titration curves can be efficiently and rigorously treated by means of a simple method, assisted by the use of logarithmic diagrams. Discusses the symmetry properties of several typical titration curves, comparing the graphical approach and an explicit mathematical treatment. (Author/JM)

Titrations are common laboratory exercises in high school and university chemistry courses, because they are easy, relatively inexpensive, and they illustrate a number of fundamental chemical principles. While students have little difficulty with calculations involving a single titration step, there is a significant leap in conceptual difficulty…

The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia.

European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients. Copyright © 2014 Elsevier Inc. All rights r