Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 54; no. 4; pp. 667 - 673
• Main Authors: Krishnaiah, Ch, Vishnu Murthy, M., Kumar, Ramesh, Mukkanti, K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.03.2011; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antipsychotic Agents - analysis; Antipsychotic Agents - radiation effects; Benzodiazepines - analysis; Benzodiazepines - chemistry; Benzodiazepines - radiation effects; Biological and medical sciences; Chromatography, High Pressure Liquid; correlation; detection limit; Drug Contamination - prevention & control; drug formulations; Drug Stability; drugs; Forced degradation; Fundamental and applied biological sciences. Psychology; General pharmacology; guidelines; Hot Temperature - adverse effects; Hydrogen-Ion Concentration; ingredients; Limit of Detection; Medical sciences; Olanzapine; Oxidation-Reduction; Pharmacology. Drug treatments; Quality Control; quantitative analysis; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Stability-indicating; Tandem Mass Spectrometry; Technology, Pharmaceutical; temperature; thermal stress; Time Factors; ultra-performance liquid chromatography; Ultraviolet Rays - adverse effects; UPLC; Validation; Validation; Stability-indicating; Olanzapine; UPLC; Forced degradation; Ultra performance liquid chromatography; Dibenzodiazepine derivatives; Atypical antipsychotic; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Chemical stability; Serotonine receptor; Determination; Thienobenzodiazepine derivatives; D2 Dopamine receptor; Storage stability; Quality control; Development; Dosage form; Active ingredient; Degradation product
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2010.10.013

A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0min. The eluted compounds were monitored at 250nm, the flow rate was 0.3mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r2>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness.