Detection and Quantitation of Nitrosamine Impurities in Drug Substances by LC-HRMS on LCMS-9030

User Benefits

- Simultaneous analysis of up to eight N-nitrosamine impurities in drug substances by LC-HRMS method on LCMS-9030. - A targeted MS/MS (TOF) method with 2 m/z isolation window by the quadrupole was optimized to obtain best sensitivity. - A mass tolerance of (±)15 ppm was adopted to produce extracted-ion chromatograms (XICs) for quantitation.

Introduction

Since 2018, the presences of N-nitrosamine impurities in some drug substances and products have been alerted by the US FDA and regulatory agencies in other countries. Nitrosamines (NSA) are toxic chemicals and some of them such as NDMA and NDEA are classified as probable human carcinogens. NDMA and NDEA were found presence first in drug substances and products of Angiotensin II receptor blockers (ARB) like losartan etc. NDMA was found in ranitidine and metformin drug products and recalls of the products occurred due to the content of NDMA above the Acceptable Intake limit (AI, 96 ng/day). Detection and quantitation of NDMA and other concerned nitrosamines at trace levels in drug products are established by using highly sensitive and selective mass spectrometry methods on GC-MS, LC-MS/MS and LC-HRMS.

July 28, 2021 GMT