A Sensitive LC-MS/MS Method for the Analysis of Azido Impurity in Losartan Drugs

User Benefits

- The highly sensitive LC-MS/MS method for the detection and quantification of azido impurities in the losartan drug substances was developed. - Four azido impurities were evaluated for linearity, LOD, LOQ, repeatability and recovery on the LCMS-8050 triple quadrupole mass spectrometer coupled with a Nexera^TM X3 LC system.

Introduction

Sartan drugs such as valsartan, losartan, and Irbesartan are high blood pressure treatments that narrow blood vessels and block the action of angiotensin II, which regulates blood pressure by causing water and salt intake. The recent discovery of N- nitrosamine impurities known as potent carcinogens in several sartan drug substances has become a global issue. In addition, the AZBT that is an azido impurity known as a mutagenic and potentially carcinogenic substance, was also detected in sartans. As a result, the European Medicine Agency(EMA) and Health Canada(HC), which are responsible for supervising medicines, have recalled some sartan drugs. Besides to AZBT, there are various types of azido impurities such as AZBC, AMBBT, and AMBBC. In this regard, the Ministry of Food and Drug Safety in Korea (MFDS) has announced the 'Test method for AZBT in sartan drug substances using LC-MS/MS’ for the analysis of AZBT, one of the azido impurities. Also, in Europe, European Directorate for the Quality of Medicines & HealthCare (EDQM) suggested the test method, ‘AZBT impurity in Valsartan, Irbesartan, Losartan, Candesartan’. In addition, the official Medicines Control Laboratory(OMCL), the research institute from the Swissmedic, introduced ‘AZBT and AZBC test methods for sartan-type drug substances using LC-MS/MS’ based on EDQM’s test method. Accordingly, this application news describes the evaluation of LC-MS/MS method for analysis of four azido impurities (AZBC, AMBBT, AMBBC and AZBT) in losartan drug substance.

June 13, 2023 GMT