A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops

Abstract

Regulatory agencies focus on the N-nitroso Drug Substance Related Impurities (NDSRIs) for the safety and efficacy of the pharmaceuticals. This study highlights the control and detection of NDSRI impurity in the broad-spectrum antibiotic moxifloxacin (MOX). The objective of the present study is to develop a highly sensitive, rapid, and novel LC-QqQ-MS/MS method for the simultaneous trace-level quantification of N-Nitroso Moxifloxacin (N-MOX) and di-Nitroso pyrrolopiperidine (DNPP) in MOX drug substance and drug products. According to the Carcinogenicity Potency Categorization Approach (CPCA), N-MOX and DNPP are classified into potency category 4, with an acceptable intake (AI) of 1500 ng/day. Chromatographic separation was achieved using a Waters Cortecs T3 C18 column (100 mm × 3.0 mm, 2.7 µm) with 0.1 % formic acid and acetonitrile as mobile phases in gradient elution mode at a flow rate of 0.3 mL/min. Triple quadrupole mass spectrometry with electrospray ionization (ESI) in multiple reaction monitoring (MRM) was used for quantification. The specific mass transitions are m/z 431.0 → 386.0 for N-MOX and 185.1 → 138.1 for DNPP. The developed method was successfully validated, and the results were within the acceptable range according to ICH guidelines. Moreover, we evaluated the eco-friendliness and greenness of the current method using enhanced tools. The results indicated a low environmental impact in terms of analysis time, solvent consumption, waste production, and sample quantity required. The method was successfully applied to quantify N-MOX in commercial MOX tablets and eye drops with a shorter run time; hence, it can quantify the presence of N-MOX and DNPP to ensure human safety and public health from using MOX formulation products.