With roughly 50% of the world population taking prescription drugs, it is important to ensure that pharmaceutical products are safe. Nitrosamine impurities have been widely publicized recently. A year ago we reported the "Valsartan crisis” which detailed the recall. In fact, nitrosamines have been found in different types of angiotensin II receptor blocker (ARB) medicines, and more recently in histamine-2 receptor blocker medicines. It is essential to analyze nitrosamines that can unintentionally occur in pharmaceutical products as they are carcinogenic impurities. The regulatory requirements demand high sensitivity to meet the low reporting limits. The analytical instrumentation must not only be sensitive but also selective to avoid false-positive non-compliant results. The stringent limits imposed by the current regulations will be lowered at the end of the interim period (April 2021), increasing the challenges for analytical science laboratories.
The U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other regulatory bodies have published several analytical methods that may be considered when determining nitrosamine content in the active pharmaceutical ingredient (API) or finished pharmaceutical product (FPP). At Thermo Fisher, we recently consolidated the methods for GC-MS analysis of nitrosamines in pharmaceutical products into a single case study. This study was published in collaboration with pharmaceutical testing labs like Laurus and SGS and looks at GC-MS and GC-MS/MS coupled with both liquid injection and headspace sampling for quantitative analysis according to the published USFDA methods and high-resolution accurate mass. The latter providing the added advantage of high selectivity and accurate mass confirmation of nitrosamines, and furthermore offers an expanded scope of analysis including options for retrospective examination of samples.