A Multi-Analyte LC–MS/MS Method for Determination and Quantification of Six Nitrosamine Impurities in Sartans like Azilsartan, Valsartan, Telmisartan, Olmesartan, Losartan and Irbesartan

化学 色谱法 奥美沙坦 甲酸 缬沙坦 大气压化学电离 检出限 替米沙坦 质谱法 化学电离 电离 有机化学 医学 离子 血压 放射科
作者
Ramana Reddy Gopireddy,Arthanareeswari Maruthapillai,Sudarshan Mahapatra
出处
期刊:Journal of Chromatographic Science [Oxford University Press]
卷期号:62 (2): 147-167 被引量:9
标识
DOI:10.1093/chromsci/bmac059
摘要

Abstract A sensitive and robust method for determination and quantification of potential genotoxic impurities in sartans has been developed. These impurities need to be controlled at trace levels during quantification in drug substances and drug products for safe consumption. Recent regulatory requirements also suggested the need to have highly sensitive analytical method for trace level quantification of nitrosamine impurities. In this paper, we have described a simple, rapid and sensitive liquid chromatography-mass spectrometry method for six potential genotoxic nitrosamine impurities: N-Nitroso dimethyl amine (NDMA), N-Nitroso diethyl amine (NDEA), N-Nitroso Ethyl Iso propylamine (NIPEA), N-Nitroso-Nmethyl-4-aminobutyric acid (NMBA) N-Nitroso diisopropylamino (NDIPA) and N-Nitroso dibutyl amine (NDBA) in Azilsartan (AZL), Valsartan (VAL), Telmisartan (TEL), Olmesartan (OLM), Losartan (LOS) and Irbesartan (IRB) with a limit of quantification of less than 0.003 ppm. Chromatographic separation is achieved using Poroshell HPH- C18, 150 × 4.6 mm, 2.7 μm column with 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at a flow rate of 0.5 mL/min using gradient mode of elution at a total run time of 20 min. Six nitrosamine impurities are ionized and quantified in positive mode of atmospheric pressure chemical ionization using multiple reaction monitoring. As per ICH guidelines, method validation is performed and evaluated the limit of quantification and detection and found to give good S/N ratios with good linearity range of 0.003–0.045 ppm with regression coefficient > 0.999 for all the six nitrosamine impurities. Method recoveries are also established using three-step sample preparation and are found to be satisfactory within 80–120%. The single method can be used routinely applied for the detection of nitrosamines in AZL, VAL, TEL, OLM, LOS and IRB.
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