Quantitation of Nitroso-Propranolol in Propranolol HCl Formulation and its Placebo Using LC-MS/MS

User Benefits

- An LC-MS/MS method for the low-level determination of Nitroso-propranolol in Propranolol HCl API and formulation - A quick easy and reliable method for NDSRI meeting regulatory requirement

Introduction

The potential for N-nitrosamine impurities in pharmaceutical products presents a challenge for the quality management of medicinal products. N-Nitrosamines are considered cohort-of-concern compounds due to the potent carcinogenicity of many of the structurally simple chemicals within this structural class. In the past 4 years, several drug products containing certain active pharmaceutical ingredients (APIs) have been withdrawn or recalled from the market due to the presence of carcinogenic low-molecular-weight N,N-dialkylnitrosamine impurities. In 2021, United States Food and Drug Administration (USFDA) received reports of certain types of nitrosamine impurities that are formed in several drug products. These nitrosamine drug substance-related impurities (NDSRIs) are a class of nitrosamines sharing structural similarity to the API (having the API or an API fragment in the chemical structure) and are generally unique to each API. NDSRIs form through nitrosation of APIs (or API fragments) that have secondary, tertiary, or quaternary amines when exposed to nitrosating compounds such as nitrite impurities in excipients and can be generated during manufacturing or during the shelf-life storage period of the drug product and substances. One such example is N-nitroso propranolol (NNP) in Propranolol API. Propranolol, a synthetic amino alcohol, is a competitive nonselective, β-adrenoreceptor antagonist extensively used to treat hypertension, angina pectoris and other cardiac diseases. Structural similarity with API and high carcinogenic potency poses great difficulties for development of low-level analytical methods for estimation of NNP in Propranolol API or formulation. This application news demonstrates an LC-MS/MS method for trace level determination of NNP in Propranolol API and formulation using an Ultra High Performance Liquid Chromatograph (UHPLC) Nexera X3 coupled with an LCMS-8060NX.

August 7, 2025 GMT