ABSTRACT
A simple, rapid, selective and stability indicating reversed phase-ultra performance liquid chromatography method was developed and validated for the simultaneous quantification of process related and degradation impurities present in Atazanavir and Ritonavir tablets. The two proposed drug components and their respective impurities were separated using Acquity BEH C18 (100 mm × 2.1 mm), 1.7 µ column at a flow rate of 0.4 mL/min. Buffer used as Mobile phase-A which consists of 0.01 M monobasic potassium hydrogen phosphate adjusted the pH to 3.6 and acetonitrile is used as organic modifier (mobile phase-B). The detector wavelength of 240 nm was used for quantifying the impurities. Both the drug components along with their impurities were eluted within a runtime of 18 min. The performance of the developed method was checked by validating the method according to the requirements of International Conference on Harmonization for parameters such as specificity, precision, linearity, ruggedness, accuracy, sensitivity (limit of detection (LOD) and limit of quantitation (LOQ)) and robustness. Linearity and range were established from LOQ level to 150% level. Accuracy of the method was demonstrated from LOQ level to 150% level. The developed stability indicating method is capable for determination of impurities of Atazanavir and Ritonavir in combined tablet dosage form as well as individual dosage forms also. The reported method enables lesser solvent consumption and reduces time and cost of the analysis in quality control laboratory.
Subject(s)
Atazanavir Sulfate/analysis , Atazanavir Sulfate/chemistry , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Ritonavir/analysis , Ritonavir/chemistry , Drug Contamination , Limit of Detection , Linear Models , Reproducibility of Results , TabletsABSTRACT
Impurities found in stressed and stability studies of olanzapine (polymorphic form-I) [1-7] in both drug substance and drug product are described. These impurities are identified as 4-(4-methyl-1-piperazinyl)-3-hydroxymethylidene-1H-benzo[b][1,4]diazepine-2(3H)-thione (hydroxymethylidene thione) and (Z)-4-(4-methyl-1-piperazinyl)-3-acetoxymethylidene-1H-benzo[b][1,4]diazapine-2(3H)-thione (acetoxymethylidene thione). An oxidative degradation pathway of olanzapine, for the formation of these impurities, has been proposed.
Subject(s)
Antipsychotic Agents/analysis , Benzodiazepines/analysis , Drug Contamination , Antipsychotic Agents/chemistry , Benzodiazepines/chemistry , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Drug Stability , Excipients/analysis , Magnetic Resonance Spectroscopy , Molecular Structure , Olanzapine , Oxidation-Reduction , Tablets , Tandem Mass Spectrometry , Technology, Pharmaceutical/methodsABSTRACT
Rivastigmine is a drug against Alzheimer's disease, and is a non-pharmacopoeial compound. During the preparation of rivastigmine in our laboratory, two impurities were detected and identified with a simple and sensitive reversed-phase liquid chromatography coupled with electrospray-mass spectrometry. The same impurities were also observed in commercial batches. These impurities were isolated by preparative HPLC and co-injected with rivastigmine sample to confirm the retention times in HPLC. These impurities were characterized as N,N-dimethyl-3-[1-dimethylaminoethyl]phenylcarboxylate (dimethyl-rivastigmine) and N,N-diethyl-3-[1-dimethylaminoethyl]phenylcarboxamide (diethyl-rivastigmine). Structural elucidation of these impurities by spectral data (1H NMR, 13C NMR and MS) is discussed.