Application of Advanced High-Resolution Mass Spectrometric Techniques for the Analysis of Losartan Potassium Drug Substance Degradation Products: From Nontargeted to Targeted Screening.

Abstract

Advances in techniques for quality analysis allow for a more detailed examination of drug impurities. High-resolution mass spectrometry (HRMS) contributes to detecting both known and unknown impurities. In this study, a combination of a nontargeted and targeted screening approach was established and applied to the detailed degradation profile of the losartan potassium (LP) drug substance. Through general unknown comparative screening (GUCS), 35 degradation products (DPs) were detected; of these, 10 DPs were confirmed with reference substances. DP-1, DP-2, DP-3, and DP-6 were the first characterized, as per previous studies; the other twenty-four were newly identified. In addition, a liquid chromatography-tandem mass spectrometry method was developed for the determination of the ten DPs. It was sensitive, with the limit of quantitation of analytes ranging from 0.01 to 0.5ng mL-1. Two newly characterized DPs, DP-1 and DP-2, were determined in active pharmaceutical ingredient solutions. This study introduced a new approach using broad screening to analyze degradation impurity profiles in LP drug substance, aiding in the identification of low-level impurities or those without reference substances. Additionally, the sensitive determination method developed allows for the precise quantification and control of ten DPs at trace levels in LP drug substances or products.