S.G. Abdullina, I.K. Petrova, R.M. Salakhova, G.K. Ziyatdinova, G.K. Budnikov

Verapamil being calcium channel-blocking agent is used for treatment of stenocardia and coronary heart disease. Constant-current coulometry is prospective method for its quantitative determination. The aim of investigation performed is development and validation of verapamil hydrochloride quantitative determination in pharmaceutical substance using coulometric titration with electrogenerated in acidic media bromine and biamperometric indication of the titration end-point. Verapamil hydrochloride reacts with electrogenerated bromine rapidly and quantitatively with participation of two electrons. Validation of verapamil hydrochloride determination has been carried out by specificity, linearity and analytical range, accuracy and reproducibility. The specificity of approach developed has been confirmed by «AddedFound» method. Relative standard deviation values (< 0.02) authenticate the absence of systematic error. Linearity of the results and analytical range has been determined by statistical treatment of data for 7 model samples on 7 levels of concentration in the interval 70-130% of verapamil hydrochloride from 100% level (250 μg in aliquot). Relationship between quantity of electricity and verapamil hydrochloride mass is linear and described with equation y=a+bx, where a=(0±6)×104, b=(39.40.2)×105 (R=0.99992). Accuracy and reproducibility of the method proposed are evaluated by comparison with results of 6 determinations on 100% level by potentiometric titration in nonaqueous media. Reproducibility of both methods has been compared using Fischer-s test. Fcalc=6.57  Ftable=10.97 at Р=99% means that difference of variances is statistically insignificant. Student-s test has been performed for the evaluation of determination accuracy (tcalc=0.25  ttable=3.17 at Р=99% and n=12). The results of experiment are not aggravated with systematic inaccuracy. Coulometric titration is valid in accuracy and reproducibility parameters. The results obtained allowed to develop method for quantitative determination of verapamil hydrochloride in tablets. Auxiliary components of tablets do not react with electrogenerated bromine and interfere the determination of acting substance.