01789nas a2200241   4500000000100000008004100001260001200042653002300054653001700077653001700094653001500111653002000126100001500146700002000161700001300181700001400194700001600208245013700224300001100361490000800372520115300380022001401533       2021                            d  c06/202110aImpurity profiling10aLC–MS/HRMS10aNitrosamines10aRifampicin10aRisk Assessment1 aWohlfart J1 aScherf-Clavel O1 aKinzig M1 aSörgel F1 aHolzgrabe U00aThe nitrosamine contamination of drugs, part 3: Quantification of 4-Methyl-1-nitrosopiperazine in rifampicin capsules by LC-MS/HRMS.  a1142050 v2033 a<p>Upon emergence of nitrosamines in various drugs, e.g in valsartan, metformin and ranitidine, 4-methyl-1-nitrosopiperazine (MeNP) was found in rifampicin in August 2020. Rifampicin is used, amongst others, for post-exposure prophylaxis of leprosy. The occurrence of MeNP can be explained by the synthesis, because 1-amino-4-methylpiperazine is concomitantly used with the organic oxidizing reagent isoamyl nitrite. According to a method reported by the FDA, the quantification of MeNP in rifampicin capsules was performed by LC-MS/HRMS. A significant contamination with MeNP was found in all samples, ranging from 0.7 to 5.1 ppm and exceeding the acceptable intake limit proposed by the FDA up to 32-fold. However, the severity of a possible leprosy infection outweighs the risks, which are concomitant with the intake of a single dose of rifampicin for post-exposure prophylaxis. Nevertheless, the extent of contamination is alarming, and countermeasures are needed to minimize public health risks. The presence of nitrosamines in rifampicin illustrates the need for better strategies in impurity profiling and compendial testing once again.</p>  a1873-264X