Methods for Analytical Control of Darunavir Tablet Dosage Forms. Part II

Previously, targeted development of special procedures regulating analytical control methods for darunavir (DRV) dosage forms showed that the use of expensive imported reference standards (RSs) could be avoided. Part I discussed such procedures and their validation results. They were intended for sections Identity; Talc, Silica, and Titania; and Dissolution of the corresponding monographs. Part II continued the examination of procedures not requiring the use of RSs that were proposed for inclusion into sections of the monographs Side Impurities and Quantitative Determination. HPLC in gradient mode was proposed for estimating the contents of side impurities. The lower limit of quantitation of a separate impurity relative to DRV was 0.02%. The relative standard deviation (RSD) of the total impurity content was less than 10%. The DRV concentration in the section Quantitative Determination was proposed to be determined by direct UV spectrophotometry of the analyte in solution (pH ~ 9) using a procedure that required preliminary experimental determination of the specific absorption coefficient (\( {A}_{1\mathrm{cm}}^{1\%} \)) of the wavelength maximum at 267 nm for DRV in aqueous MeOH solutions (pH ~ 9). The experimental \( {A}_{1\mathrm{cm}}^{1\%} \)) = 393.4 cm–1 (RSD < 1% at confidence level á = 0.05). Therefore, \( {A}_{1\mathrm{cm}}^{1\%} \)) was a physicochemical constant. The RSD of results could be reduced to 1% and the analysis time shortened by 2 – 3 times because the preparation of RS solutions and measurements of their optical densities were obviated if \( {A}_{1\mathrm{cm}}^{1\%} \)) was used for quantitative determinations of DRV by direct UV spectrophotometry.