METHOD DEVELOPMENT AND VALIDATION BY GC-MS FOR QUANTIFICATION OF 1-CHLOROETHYL CYCLOHEXYL CARBONATE AS A GENOTOXIC IMPURITY IN CANDESARTAN CILEXETIL DRUG SUBSTANCE
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2014, Vol 6, Issue 11
Abstract
Objective: Candesartan Cilexetil is an Angiotension II receptor antagonist used mainly for the treatment of hypertension. The synthesis process of Candesartan uses 1-Chloroethyl Cyclohexyl Carbonate (CECC), which is potential genotoxic impurity as per the EMEA guideline. The method development and later validation activity was proposed and performed for the analysis of 1-Chloroethyl Cyclohexyl Carbonate (CECC) in Candesartan Cilexetil drug substance. Based on daily dose basis evaluation limit required was 0.49 µg/mL (i. e. 49 µg/g).Methods: The development activity was conducted by Gas chromatography technique with Mass spectrometer as detector. DB-5 make Agilent J&W column with length 50 meter, internal diameter 0.32 mm, film thickness 0.52 µm was used. Phase of DB-5 is 5% phenyl, 95% dimethyl polysiloxane and is an intermediate polarity phase with very good selectivity for polar compounds. Hexane was selected as diluent considering the selective solubility of CECC. Results: Validation activity was planned and completed based on the International Conference on Harmonization (ICH) guidelines. The LOD and LOQ values were found to be 0.70 and 2.11 µg/g (i. e. 0.007 and 0.021 µg/mL) for CECC. Method very sensitive as method was related to genotoxic impurity. Also accuracy results were well in the range of 99 to 105 %. Linearity curve showed correlation coefficient of 0.99997.Conclusion: From validation data it was confirmed that the method is specific, precise, accurate, linear and sensitive for the required purpose. During the same activity three commercial batches were analyzed. Validation data as well as commercial batch data was enough to prove the method suitability.Â
Authors and Affiliations
Nalavade Atul Kakasaheb, Ramakrishna K. , Srinivasarao V.
Keywords
Related Articles
- EP ID EP579323
- DOI -
- Views 97
- Downloads 1
THYMOL TEMPERS As (III) AND Hg (II) CAUSED HYPERCONTRACTILITY BY SIMILAR PATHWAYS IN ISOLATED AORTIC AND TRACHEAL RINGS
Objective: Thymol is known to cause smooth muscle relaxation, possibly by inhibition of Ca2+influx, release or loss of its sensitivity. It is, however, also reported to be a strong antioxidant in several other systems. I...
AMELIORATION OF STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA AND DYSLIPIDEMIA THROUGH ALOE DEBRANA
Objective: To study the antiglycemic and antidyslipidemic effects of an ethanolic extract of Aloe debrana leaf gel extract in streptozotocin-induced diabetic rats.Methods: A. debrana leaves were collected from Enemore di...
SYNTHESIS, ANTITUMOR ACTIVITY, PHARMACOPHORE MODELING AND QSAR STUDIES OF NOVEL PYRAZOLES AND PYRAZOLO [1, 5-A] PYRIMIDINES AGAINST BREAST ADENOCARCINOMA MCF-7 CELL LINE
Objective: The present work aimed to synthesize New series of pyrazoles 3 and pyrazolo[1,5-a]pyrimidines 5, 7, 9 in order to evaluate their antiproliferative activity against human breast adenocarcinoma MCF-7cell line an...
SEROPREVALENCE AND GENOTYPING OF HEPATITIS C VIRUS AMONG HOSPITAL BASED GENERAL POPULATION IN VIJAYPUR, INDIA
Objective: Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. According to World Health Organization (WHO) there are 180 million people affected wit...
PHYSICOCHEMICAL, PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ANTIBACTERIAL ACTIVITY AGAINST CLINICAL PATHOGENS OF MEDICINALLY IMPORTANT ORCHID GEODORUM DENSIFLORUM (LAM) SCHLTR
Objective: To evaluate the Physicochemical, Preliminary Phytochemical analysis and Antibacterial activity of Geodorum densiflorum against clinical pathogens and to prove the orchid will target to meet the therapeutic dem...