Eco‐Friendly LC–MS/MS Determination of N ‐Nitroso Vildagliptin Amide, a Nitrosamine Carcinogenic Impurity, in Vildagliptin Drug Substance Using Advanced Greenness Metrics

ABSTRACT

In the process of making vildagliptin (VG) API, one of the nitrosamine groups found in the drug is N ‐nitroso vildagliptin amide (NVA). This led to the development of a multi‐reaction monitoring (MRM) approach that is both sensitive and reliable for quantitatively assessing NVA impurity in VG API. Using isocratic eluent conditions, the Shim‐pack GIST C18 column (250 mm × 4.6 mm, 5 µm) was used to separate VG and NVA. The mobile phase utilized in this study was a mixture of 0.1% formic acid in water and methanol in a ratio of 65:35 v/v. With a flow rate of 0.8 mL/min, the mobile phase runs. The transition for NVA's MRM is 351.00 > 115.30 at a collision energy of −11.0 eV. In this study, the values of 0.5 and 1.5 ppb, respectively, were used to verify the limits of detection and quantification for NVA impurity. The findings showed an accuracy level between 80% and 120% for limit of quantification (LOQ)‐spiked samples and 85%–115% for 50%, 100%, and 150% spiked samples. Ultimately, the devised technique of liquid chromatography tandem mass spectrometry provides an accurate, linear, appropriate, and exact way to assess the NVA impurity in the VG API. Several environmental impact evaluation tools were used to determine how eco‐friendly this method is. These included the analytical eco‐scale, the analytical greenness (AGREE) tool, the AGREE metric approach, the national environmental method index (NEMI), and the modified green analytical procedure index (MoGAPI). The devised approach has an Eco‐Scale score of 73, MoGAPI score of 72, and an AGREE score of 0.6.