Analytical Control of Darunavir Tablet Dosage Forms. Part I.

Abstract

Purposeful development of special methods to be included into pharmacopoeial monographs on the quality of darunavir (DRV) preparations is shown to allow the use of expensive imported standard samples (SSs) for drug analysis to be avoided. Part I of the present work describes these methods and their validation. UV spectrophotometry is proposed in the “Authenticity” section for detecting DRV by the coincidence of extrema in the spectrum of an aqueous MeOH extract (pH 9) with well-known peaks in the spectrum of deprotonated DRV at 230 nm (minimum) and 267 nm (maximum). This section also requires GC analysis for solvated EtOH, the presence of which indicates that DRV ethanolate was used as the active pharmaceutical ingredient (API) and the absence of which, that non-solvated amorphous DRV was used. The significant increase in the accuracy of the quantitative determination and the sharp reduction in its duration allow the use of SSs to be avoided. For this reason, the “Dissolution” section proposes determining the DRV concentration in the dissolution medium (pH 3) by spectrophotometry using a method that requires experimental determination of the specific absorption coefficient $$ \left({A}_{1\mathrm{cm}}^{1\%}\right) $$ of DRV solutions in this medium at the maximum (267 nm). The established value $$ \left({A}_{1\mathrm{cm}}^{1\%}\right. $$ = (393.4 ± 2) cm–1 was a physicochemical constant with a relative standard deviation RSD < 1% at confidence level α = 0.05.