Earth-friendly spectrophotometric methods for simultaneous determination of ledipasvir and sofosbuvir: Application to average content and uniformity of dosage unit testing.

Simple, rapid, sensitive, accurate, precise and earth-friendly spectrophotometric methods were developed for the simultaneous analysis of ledipasvir (LED) and sofosbuvir (SOF) without interference of both sunset yellow dye and copovidone excipients (the most probable interferents) in their combined dosage form. These proposed methods were based on measurement of LED in synthetic mixtures and combined dosage form by first derivative (1D) spectrophotometry at 314 nm over the concentration range of 2-50 µg mL-1 with coefficient of determination (R2) > 0.9999, mean percentage recovery of 99.98 ±â€¯0.62. On the other hand, SOF in synthetic mixtures and combined dosage form was determined by five methods. Method I is based on the use of 1D spectrophotometry at 274.2 nm (zero crossing point of LED). Method II involves the application of conventional dual wavelength method (DW) at the absolute difference between SOF zero order amplitudes at 261 nm (λmax of SOF) and 364.7 nm. At these wavelengths, the absolute difference between LED zero order amplitudes was observed to equal zero. Method III depends on isosbestic point method (ISP) in which the total concentration of both drugs was measured at isosbestic point at 262.7 nm. Concentration of SOF could be obtained by subtraction of LED concentration. While, method IV depends on absorbance correction method (absorption factor method), which is based on determination of SOF concentration at 262.7 nm (λISP) and LED at 333 nm (λmax of LED). Finally, method V depends on absorbance ratio method (Q-analysis) in which 262.7 nm (λISP) and 261 nm (λmax of SOF) were selected to determine SOF concentration. The linearity range for all methods for SOF determination was 2-50 µg mL-1 with coefficient of determination (R2) > 0.9999. Methods I, II & III were also applied for determination of SOF concentration in single dosage form. Their mean percentage recoveries were 100.35 ±â€¯1.85, 99.97 ±â€¯0.54 and 100.03 ±â€¯0.49, for the three methods respectively. The proposed methods were validated according to international conference of harmonization (ICH) requirements and statistically compared to published reference methods. The ANOVA test confirmed that there is no significant differences between the proposed methods, and can be used for routine analysis of LED and SOF in commercial tablets. These developed methods were applied to estimate the average content and uniformity of dosage unit for LED/SOF combined dosage form and SOF single dosage form according to British pharmacopeia (BP) requirements.

Application of π acceptors to the spectrophotometric and spectrofluorimetric determination of vincamine and naftidrofuryl oxalate in their pharmaceutical preparations.

Three different spectrophotometric and two spectrofluorimetric methods have been developed and validated for the determination of vincamine (VN) and naftidrofuryl oxalate (NF) in tablets. The spectrophotometric methods depend on charge transfer complex formation between each of VN and NF with 7,7,8,8-tetracyano-quinodimethane (TCNQ), 2,6-dichloroquinone-4-chloroimide (DCQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) at 843, 580 and 588 nm, respectively. The spectrofluorimetric methods are based on the formation of charge transfer complex between each of the two drugs and TCNQ, with measurement of the fluorophore formed at 312/375 and 284/612 nm, respectively, or with DDQ at 400/475 and 284/396 nm, respectively. In the spectrophotometric measurements, Beer's law was obeyed at concentration ranges of 1.5-16, 10-180 and 12-140 µg/ml for VN with TCNQ, DCQ, and DDQ, respectively. For NF, the corresponding concentrations were 2-28, 5-75 and 25-150 µg/ml with TCNQ, DCQ, and DDQ, respectively. In the spectrofluorimetric measurements, the ranges for VN were 0.05-0.9 and 0.3-4 µg/ml with TCNQ and DDQ, respectively, whereas for NF the ranges were 0.05-0.85 and 0.5-8 µg/ml with TCNQ and DDQ, respectively. The different experimental parameters affecting the development and stability of the formed color or fluorophore were studied and optimized and the molar ratios of the complexes were calculated. The proposed methods were validated according to ICH guidelines and were successfully applied for the determination of VN and NF in their tablet dosage forms.