Kinetic assay of D-Penicillamine in pure and pharmaceutical formulations based on ligand substitution reaction

A kinetic analytical method using uncatalyzed ligand substitution reaction and spectrophotometeric monitoring for the quantification of D-pencillamine (D-PA) i.e. 2-amino-3-mercapto-3-methylbutanoic acid or β,β-dimethylcysteine or 3-mercaptovaline or 3-mercapto-D-valine in pure as well as dosage forms has been validated and applied. The method is based on the uncatalyzed ligand substitution reaction between [Fe(CN)5(H2O)]3− and D-PA which produces the complex [Fe(CN)5(D-PA)]3−. The substituted complex [Fe(CN)5(D-PA)]3− shows an absorption maximum at 421 nm. The proposed method shows good linear dynamic range of 14.92–149.21 μg mL− 1. By measuring the fixed time absorbance as a measure of initial rate of the complex formation during the course of the reaction at this wavelength, D-PA can be determined in the range 14.92–149.21 μg mL− 1. The recoveries of D-PA from various samples spiked at the usage level have been quantitative. The limit of quantification (3σ) was determined as 5.16, 3.68 and 3.13 μg mL− 1 of D-PA corresponding to the fixed time of 2, 3 and 5 min respectively. The common excipients used as additives in pharmaceuticals did not interfere in the proposed method. The method was successfully employed for the analysis of D-PA content in commercial pharmaceutical preparations (tablets) and revealed quantities almost equal to those measured using the standard method, and demonstrated good accuracy and precision. The proposed method is rapid, simple, accurate and precise without the need for authentic analyte standards. It could therefore be used as an alternative to the quantification of D-PA in various samples.

► A method using uncatalyzed ligand substitution reaction and spectrophotometeric monitoring was applied and validated to determine D-PA in tablets. ► This method has good accuracy, precision, selectiveness and linearity. ► The proposed method is more rapid and simple. ► We found that the proposed method is reliable for the accurate determination of D-PA. ► This method can be used for the monitoring of D-PA in drug formulations.