Kareti Aparna Devi, V. Hanuman Reddy, Gaddam Thirupathi Reddy, Krishna Kumari Avula, Yellala Venkata Rami Reddy
ABSTRACT Regulatory agencies emphasize stringent control of N ‐nitrosamine drug substance–related impurities to ensure the safety and efficacy of pharmaceutical products. The present study focuses on the detection and control of N ‐nitrosamine impurities in the antidiabetic drug teneligliptin. The primary objective was to develop a rapid, highly sensitive, and novel liquid chromatography triple quadrupole mass spectrometry method for the simultaneous trace‐level quantification of N ‐nitroso teneligliptin ( N ‐NTNG) and N ‐nitroso Boc‐piperazine ( N ‐NBP) in TNG drug substance and finished dosage forms. Based on the Carcinogenicity Potency Categorization Approach, both N ‐NTNG and N ‐NBP are classified under potency Category 4 and 3, with an acceptable intake (AI) limit of 1500 and 400 ng/day, respectively. Chromatographic separation was achieved on a Waters Cortecs T3 C18 column (100 × 3.0 mm, 2.7 µm) with 0.1% formic acid and acetonitrile as mobile phases, applied in gradient elution at a flow rate of 0.3 mL/min. Quantification was performed using triple quadrupole mass spectrometry with electrospray ionization in multiple reaction monitoring mode. The selected mass transitions were m / z 456.15 → 310.25 (quantifier) and 456.15 → 243.16 (qualifier) for N ‐NTNG, and m / z 160.09 → 130.07 (quantifier) and 160.09 → 55.96 (qualifier) for N ‐NBP. The developed method was successfully validated in accordance with ICH guidelines, with all validation parameters meeting acceptance criteria. The method was effectively applied to the quantification of N ‐NTNG and N ‐NBP in commercial TNG tablets, offering a reduced run time and high sensitivity. Consequently, the proposed method is suitable for routine monitoring of NDSRI impurities, thereby supporting in the safeguarding of human health and the public in the use of teneligliptin formulations.