Chem. Pharm. Bull. 55(12) 1655—1661 (2007)

tidepressants, a group of drugs widely used for treating depressive diseases. Its chemical structure is shown in Fig. 1. Most existing methods for the determination of nortriptyline in bulk, pharmaceutical formulations and biological samples have been reviewed. Among other methods described for the assay of this drug are direct UV-spectrophotometry, derivatives spectrophotometry, fluorimetry and colourimetry. The colourimetric methods involve ion association complex with dye—Light Green FCF at pH 5 and Orange II at pH 2 or charge-transfer complex with 7,7,8,8tetracyanoquinodimethane (TCQN). Extractive spectrophotometric procedures are popular for their sensitivity in the assay of drugs and, therefore, ion-pair extractive spectrophotometry has received considerable attention for the quantitative determination of many pharmaceutical compounds. Quantitative analysis of the drugs applying extractive spectrophotometric methods is mainly founded on such factors as type of solvent extraction, nature of coordination agents, acidity of the solution, concentration of reagents, temperature, time of reaction and extraction. Some methodological reports for the determination of nortriptyline using specrophotometry have been published. However, these methods have several disadvantages in terms of cost performance, consumption of time and essential equipment, difficult reaction conditions and procedures for determination of drugs. For example, De La Pena et al. developed a fast kinetic method for the determination of nortriptyline in pharmaceutical preparations by use of photometric and fluorimetric detection. But the applied procedures required a temperature of 50 °C for both types of detection. Obtained linear dynamic ranges of the drug determinations were too broad. Another method was based on oxidation of imipramine and desipramine (drugs related to nortriptyline) with ammonium metavanadate. The method has been developed for determination of the drugs in the visible (VIS) range. However, the applied oxidizing agent cannot be used for determination of nortriptyline in the VIS range. The drug oxidation product is colourless and ammonium metavanadate is an unsuitable agent for its production. Oztunc et al. have proposed a method for nortriptyline determination which exhibited disadvantages in terms of difficult reaction conditions. In this procedure maximum absorption was reached at 80 °C and heating time of 10 min was recommended for maximum intensity colour development. Most of the proposed agents for spectrophotometric determination of nortriptyline and related drugs are unsatisfactory for different reasons, e.g., a long period for maximum intensity color development, lengthy and difficult procedure, lack Sensitive Extractive Spectrophotometric Methods for the Determination of Nortriptyline Hydrochloride in Pharmaceutical Formulations