Hydrolytic Degradation Study of Lansoprazole, Identification, Isolation and Characterisation of Base Degradation Product

Lansoprazole degradation is accelerated in both acidic and basic medium in water. The present investigation deals with the hydrolytic degradation of Lansoprazole. Acidic medium degradation show all known impurities and degradation products whereas basic degradation studies show new impurity which has higher molecular weight than Lansoprazole. New impurity was identified, isolated using mass based auto purification system and characterised by 1H NMR, 13C NMR, HMBC, HSQC, NOE, COSY and HRMS experiments. Isolated impurity was showing molecular weight of 467.10, molecular formula of C23H16F3N5OS and its name is 7-(3-Methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl)-7H-benzo[4,5]imidazo[2,1-b]benzo[4,5]imidazo[2,1-d][1,3,5]thiadiazine.

A Stability Indicating Reverse Phase-HPLC Method Development and Validation for the Estimation of Rucaparib in Bulk and Pharmaceutical Dosage Form

The research was carried out for establishing a new reverse phase-HPLC stability indicating method for the quantification of Rucaparib. The experiment was determined on Waters HPLC instrument using 996 photo-diode array detector. The separation was done by using symmetry C-18 ODS (25 cm × 0.46 cm internal diameter) 5 μm analytical column containing mobile phase of Phosphate buffer (0.02 M) and methanol [65:35% v/v] adjusted pH to 4.8 by adding dilute ortho phosphoric acid. The method was run at 1 ml·min-1 at 286 nm detection. The drug was eluted at 5.484 min. After developing the method, it was assured for the intended use by validation which was done according to ICH Q2B guidelines. The analytical parameters checked were linearity, accuracy, repeatability, intermediate precision, limit of detection, limit of quantitation, ruggedness and robustness. It was observed that the response of the detector was linear in the range of 6 - 14 μg/ml with correlation coefficient of 0.999. The results of all the parameters were found to be within the acceptance criteria. The stability indicating assay method was established by using the samples generated by forced degradation process. The forced degradation was carried out by subjecting the drug to acid, alkali, thermal, oxidative and photolytic degradation and the results showed that the degradation products were successfully separated from the drug. Hence, this can be applied perfectly later for the analysis of quality of the rucaparib drug.

Identification, Isolation and Characterization of Unknown Acid Degradation Product of Nevirapine

A Novel stability indicating RP-UPLC chromatographic method was developed for analysis of Nevirapine in pharmaceutical formulations. The developed RP-UPLC method is superior in technology to conventional RP-HPLC with respect to speed, resolution, solvent consumption and cost of analysis. Nevirapine was subjected to the stress conditions like acid, base, thermal, oxidative and photolytic degradation. Nevirapine was found to degrade significantly in acid and thermal degradation. In acid degradation relative retention time with 0.42 is found as unknown impurity. New impurity was identified, isolated using mass based auto purification system and characterized by 1H NMR (1D and 2D) and HRMS experiments. Isolated impurity was showing molecular weight of 244.10, molecular formula C12H12N4O2 and its name as 2-(3-Amino-4-methylpyridin-2-ylamino)nicotinic acid. The calibration graph was linear and the method showed less deviation in accuracy results. The test solution was found to be stable for 20 days when stored in the refrigerator between 2°C to 8°C. The developed RP-UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines. The intra-day and inter-day variation was less than 1%. The method was reproducible and selective for the estimation of Nevirapine. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating method.

Identification, Isolation and Structure Confirmation of Forced Degradation Products of Sofosbuvir

A new stability indicating reverse phase chromatographic method was developed for the analysis of Heptisis C Drug Sofosbuvir. The developed UPLC method was superior in technology to conventional RP-HPLC with respect to resolution, speed, solvent consumption and analysis cost. Sofosbuvir was subjected to the thermal, hydrolytic, oxidative, and photolytic degradation, according to ICH guidelines. The drug depicted degradation in acidic, basic and oxidative conditions and it was stable to other stress conditions (thermal and photolytic). Identified degradation products were isolated using mass supported auto purification system and characterized by NMR techniques (1H NMR, D2O Exchange, 13C NMR, 31P NMR, 19F NMR, HSQC and HMBC) and HRMS experiments. Isolated acid degradation impurity was showing molecular weight of 416.08, molecular formula C16H18FN2O8P and its name as (R)-((2R, 3R, 4R, 5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methyl phenyl hydrogen phosphate. Isolated base degradation impurity-A was showing molecular weight of 453.13, molecular formula C16H25FN3O9P and its name as (S)-isopropyl 2-((R)-(((2R, 3R, 4R, 5R)-5-(2, 4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoate. Isolated base degradation impurity-B was showing molecular weight of 411.08, molecular formula C13H19FN3O9 P and its name as (S)-2-((R)-(((2R, 3R, 4R, 5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methox-y)(hydroxy)phos-phorylamino)propanoic acid. In oxidative degradation study, degradation was observed very less and with obtained quantity (less than 2 mg) recorded 1H NMR and HRMS analysis. From the spectral data degradation product was showing molecular weight of 527.15, molecular formula C22H27FN3O9P and its name as (S)-isopropyl 2-((S)-(((2R, 4S, 5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-4-methyl-3-oxotetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate. The developed chromatographic method was validated as per ICH guidelines and proved suitable for the stability testing and quality control of the drug Sofosbuvir