Guest Author: Phil Koerner, PhD.
The U.S. Food and Drug Administration (USFDA) and The European Medicines Agency (EMA) have set legally-binding limits for nitrosamine impurities in sartan blood pressure medicines. On their website, the EMA states that “companies must now take measures to avoid the presence of these impurities and carry out rigorous testing of their products.” This has increased the need for chromatographic testing methods, along with several LC-MS and GC-MS methods being published.
The SCIEX APAC Applications Support Center in Beijing, China has recently published an application note for the rapid analysis of eight genotoxic nitrosamines by HPLC-MS/MS with a reported LLOQ (lower limit of quantitation) of 0.1 ng/mL, equivalent to 0.05 µg/g of impurity in the drug product. This is lower than the threshold of toxicological concern defined by the EMA and USFDA. You can click the image below or the following link to see the full analysis: CLICK HERE
The EMA continues to closely monitor drug manufacturing, and as a precaution, has recently called on companies using certain reagents to manufacture pioglitazone, a diabetes drug, to test their products and check their processes to rule out the presence of nitrosamine impurities, in particular nitrosodimethylamine (NDMA). This follows the detection of low levels of NDMA in a few batches of pioglitazone manufactured by Hetero Labs in India.
In March of this year, Hetero announced a recall of 87 lots of losartan potassium tablets, which had been found to contain another nitrosamine impurity NMBA (N-Nitroso-N-methyl-4-aminobutyric acid). This impurity is a known animal and potential human carcinogen. Shortly after, Torrent and Teva recalled losartan in the US due to the presence of NMBA in the API manufactured by Hetero, which exceeded the USFDA’s interim acceptable exposure limit of 9.82 ppm. More recently, another nitrosamine, N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), was reported in losartan potassium tablets, resulting in the product also be recalled from the market.
These sartan drug medicine recalls have been necessary because the exposure to genotoxic nitrosamines poses an unacceptable safety risk to patients. However, it has resulted in a shortage of these drugs as well. To keep up with the latest news on the topic, you can visit the FDA website: CLICK HERE, or the EMA website: CLICK HERE
And if you are interested in a deeper dive into sartan drugs, check out our earlier article, “Sartan Drugs Have Been Deemed in Shortage by the FDA”, which focuses on the make-up and how sartan drugs could affect you.