Manal S. Elmasry

Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure form, human plasma and human urine using micellar monolithic HPLC-UV method and application to pharmacokinetic study

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. Separation and quantitation were carried out on anonyx™ C8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 μL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50-400, and 40-400 ng/mL, respectively in pure form, 60-300 and 50-300 ng/mL, respectively for human plasma and over 50-400, and 40-400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences.

Comparative study of six sequential spectrophotometric methods for quantification and separation of ribavirin, sofosbuvir and daclatasvir: An application on Laboratory prepared mixture, pharmaceutical preparations, spiked human urine, spiked human plasma, and dissolution test

In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7 nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8 nm, and mean centering of the ratio spectra (MCR) at 224 nm and 258 nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) μg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.

Multivariate analysis of tioconazole — TCNQ charge transfer interaction: Kinetics, thermodynamics and twofold response optimization

Charge-transfer complex (CTC) formation between tioconazole (TCZ) as an n-electron donor and 7, 7, 8, 8-tetracyanoquinodimethane (TCNQ) as a π-acceptor was studied spectrophotometrically with an accompanying kinetic and thermodynamic investigation. Multivariate data analysis via a set of experimental designs was executed for this purpose. A 23 - two-level full factorial design (FFD) was used for inspecting the proposed variables while a face-centered central composite design (FCCCD) was used to adjust the levels of variables proved to be significant. Two responses were quantified as a result of this interaction; complex I (Y1, measured at 743 nm) and complex II (Y2, measured at 842 nm). Derringers function and overlaid contour plots were used to concurrently optimize both responses. Benesi-Hildebrand equation was applied to determine of formation constant (K), and the molar absorptivity (Ɛ) of the formed complex. Different thermodynamic parameters; the standard Gibbs free energy change (∆G°), the standard enthalpy of formation (∆H°) and the standard entropy change (∆S°) were determined for the reaction product. The proposed method was validated regarding the linearity, intra-, and inter-day precision and accuracy, limit of detection, limit of quantification and following the ICH standards. The proposed method was also applied for the determination of TCZ in its pharmaceutical preparations. Having a higher molar absorptivity and higher formation constant, complex II was of choice for all subsequent measurements. Application of Benesi-Hildebrand equation supported the formation of 1: 1 CTC. Thermodynamic study revealed the endothermic characters and the spontaneity of formation of the CTC at high temperature.