Quantitative Determination of NDMA Impurity in Ranitidine Drug Products – Examples of Actual Samples Analysis by LCMS-8060 with APCI

User Benefits

- A high sensitivity MRM based method was established for quantitative determination of NDMA in ranitidine API and drug products on LCMS-8060. - The method performance such as LOD, LOQ, repeatability and specificity was evaluated in reference to the FDA method published in 2019.

Introduction

On 13 September 2019, the US FDA released first alert on the presence of N-nitrosodimethylamine (NDMA) impurity, classified as a human carcinogen, in some ranitidine drug products. It was revealed voluntary recalls of 14 lots of ranitidine capsules by Sandoz Inc., in the FDA Updates issued on 24 Sep 2019, due to NDMA impurity found in the products. The US FDA has advised companies to recall ranitidine drugs if testing shows levels of NDMA above the acceptable daily intake, i.e., 96 nanograms per day (ng/day) or 0.32 parts per million (ppm) for ranitidine. In October 2019, the US FDA released testing methods of NDMA impurity in ranitidine solid by LC-HRMS and LC/MS/MS (TQ) method. This Application News describes a high sensitivity and robust LC/MS/MS method used for quantitative determination of NDMA in ranitidine substances and drugs obtained from manufacturers. The sample preparation procedure, system suitability, identification and calculation follows the FDA method with certain modifications.

September 24, 2021 GMT