An Overview of Titrimetry


Titrimetry refers to a group of methods of quantitative analysis to determine the concentration of an identified analyte.

The USP general chapter <541> Titrimetry is currently divided into the following main sections:

  1. Direct titrations
  2. Residual titrations
  3. Complexometric titrations
  4. Oxidation-reduction (Redox) titrations
  5. Titrations in nonaqueros solvents
  6. Indicator and potentiometric endpoint detection
  7. Blank corrections


Direct titration is the treatment of a soluble substance, contained in solution in a suitable vessel (the titrate), with an appropriate standardized solution (the titrant), the endpoint being determined instrumentally or visually with the aid of a suitable indicator.


Some Pharmacopeial assays require the addition of a measured volume of a volumetric solution, in excess of the amount actually needed to react with the substance being assayed, the excess of this solution then being titrated with a second volumetric solution. This constitutes a residual titration and is known also as a “back titration”.


Successful complexometric titrations depend on several factors. The equilibrium constant for formation of the titrant-analyte complex must be sufficiently large that, at the endpoint, very close to 100% of the analyte has been complexed. The final complex must be formed rapidly enough that the analysis time is practical. When the analytical reaction is not rapid, a residual titration may sometimes be successful.


Determinations may often be carried out conveniently by the use of a reagent that brings about oxidation or reduction of the analyte. Many redox titration curves are not symmetric about the equivalence point, and thus graphical determination of the endpoint is not possible; but indicators are available for many determinations, and a redox reagent can often serve as its own indicator. As in any type of titration, the ideal indicator changes color at an endpoint that is as close as possible to the equivalence point.


Acids and bases have long been defined as substances that furnish, when dissolved in water, hydrogen and hydroxyl ions, respectively. This definition, introduced by Arrhenius, fails to recognize the fact that properties characteristic of acids or bases may be developed also in other solvents.

A more generalized definition is that of Brönsted, who defined an acid as a substance that furnishes protons, and a base as a substance that combines with protons. Even broader is the definition of Lewis, who defined an acid as any material that will accept an electron pair, a base as any material that will donate an electron pair, and neutralization as the formation of a coordination bond between an acid and a base.

The endpoint may be determined visually by color change, or potentiometrically, as indicated in the individual monograph. If the calomel reference electrode is used, it is advantageous to replace the aqueous potassium chloride salt bridge with 0.1 N lithium perchlorate in glacial acetic acid for titrations in acidic solvents or potassium chloride in methanol for titrations in basic solvents.


The simplest and most convenient method by which the equivalence point, i.e., the point at which the stoichiometric analytical reaction is complete, may be determined is with the use of indicators. These chemical substances, usually colored, respond to changes in solution conditions before and after the equivalence point by exhibiting color changes that may be taken visually as the endpoint, a reliable estimate of the equivalence point.

A useful method of endpoint determination results from the use of electrochemical measurements. If an indicator electrode, sensitive to the concentration of the species undergoing titrimetric reaction, and a reference electrode, whose potential is insensitive to any dissolved species, are immersed in the titrate to form a galvanic cell, the potential difference between the electrodes may be sensed by a pH meter and used to follow the course of the reaction. Where such a series of measurements is plotted correctly (i.e., for an acid-base titration, pH versus mL of titrant added; for a precipitimetric, complexometric, or oxidation-reduction titration, mV versus mL of titrant added), a sigmoid curve results with a rapidly changing portion (the “break”) in the vicinity of the equivalence point. 

The midpoint of this linear vertical portion or the inflection point may be taken as the endpoint. The equivalence point may also be determined mathematically without plotting a curve. However, it should be noted that in asymmetrical reactions, which are reactions in which the number of anions reacting is not the same as the number of cations reacting, the endpoint as defined by the inflection of the titration curve does not occur exactly at the stoichiometric equivalence point.

Thus, potentiometric endpoint detection by this method is not suitable in the case of asymmetric reactions, examples of which are the precipitation reaction and the oxidation-reduction reaction.

All acid-base reactions, however, are symmetrical. Thus, potentiometric endpoint detection may be employed in acid-base titrations and in other titrations involving symmetrical reversible reactions where an indicator is specified, unless otherwise directed in the individual monograph.

Two types of automatic electrometric titrators are available. The first is one that carries out titrant addition automatically and records the electrode potential differences during the course of titration as the expected sigmoid curve. In the second type, titrant addition is performed automatically until a preset potential or pH, representing the endpoint, is reached, at which point the titrant addition ceases.


As previously noted, the endpoint determined in a titrimetric assay is an estimate of the reaction equivalence point. The validity of this estimate depends upon, among other factors, the nature of the titrate constituents and the concentration of the titrant. An appropriate blank correction is employed in titrimetric assays to enhance the reliability of the endpoint determination. Such a blank correction is usually obtained by means of a residual blank titration, wherein the required procedure is repeated in every detail except that the substance being assayed is omitted. In such instances, the actual volume of titrant equivalent to the substance being assayed is the difference between the volume consumed in the residual blank titration and that consumed in the titration with the substance present. The corrected volume so obtained is used in calculating the quantity of the substance being titrated, in the same manner as prescribed under Residual Titrations. Where potentiometric endpoint detection is employed, the blank correction is usually negligible.

In the Pharmacopeial Forum, PF 48(5), a revision of USP chapter <541> Titrimetry is being proposed. The proposal is based on the version of the chapter official prior to 2013.

According to the proposal, the chapter will be restructured into only three sections:

  1. Introduction
  2. Types of titrations
  3. Materials and equipment

Reference: USP chapter <541> Titrimetry

Read also: Karl Fischer Titration in Pharmaceutical Industry

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