Green liquid chromatography mass spectrometry method for determination of n-methyl-n-benzylnitrosamine (carcinogenic impurity) in lacosamide drug substance by advance metrics

IF 4.9 2区化学 Q1 CHEMISTRY, ANALYTICAL

Microchemical Journal Pub Date : 2025-02-26 DOI:10.1016/j.microc.2025.113175

Yerramreddy Srilatha , Kousrali Sayyad , Leela Prasad Kowtharapu , Magapu Ravi Kumar , N. Ramakrishna Reddy , Loka Subramanyam Sarma

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引用次数: 0

Abstract

N-Methyl-n-benzylnitrosamine (MBNA) is one of the nitrosamine moiety present in lacosamide, during the manufacturing of lacosamide active pharmaceutical ingredient (API). As a result, a sensitive and reliable technique featuring multi reaction monitoring method has been developed for the quantitative assessment of MBNA impurity in the lacosamide API. The separation of lacosamide and MBNA obtained with a Zorbax SB-Phenyl (250 × 4.6 mm, 5 µm) column under gradient eluent conditions. 0.1 % formic acid in water and 0.1 % formic acid in methanol were used as mobile phases A and B, respectively, in the current study. The mobile phase flow rate is 0.8 mL min⁻¹. The multi-reaction monitoring transition for MBNA is 151.00 > 91.20 at a collision energy of −12.0 eV. The limit of detection and limit of quantification concentrations were validated with 0.0015 ppm and 0.0045 ppm, respectively for MBNA impurity in the current study. The accuracy results were lies within the range of 70 %–130 %. Eventually, the developed liquid chromatography tandem mass spectrometry method offers a linear, accurate, suitable, and precise approach to estimate the MBNA impurity present in the lacosamide API.The environmental friendliness of this method was assessed using the national environmental method index (NEMI), the modified green analytical procedure index (MoGAPI), the complex modified green analytical procedure index (Complex MoGAPI),the analytical greenness (AGREE) tool, and the analytical eco-scale. The AGREE score and the eco-scale score of the developed method was found to be0.61 and 67, respectively.

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来源期刊

Microchemical Journal 化学-分析化学

CiteScore

8.70

自引率

8.30%

发文量

1131

审稿时长

1.9 months

期刊介绍： The Microchemical Journal is a peer reviewed journal devoted to all aspects and phases of analytical chemistry and chemical analysis. The Microchemical Journal publishes articles which are at the forefront of modern analytical chemistry and cover innovations in the techniques to the finest possible limits. This includes fundamental aspects, instrumentation, new developments, innovative and novel methods and applications including environmental and clinical field. Traditional classical analytical methods such as spectrophotometry and titrimetry as well as established instrumentation methods such as flame and graphite furnace atomic absorption spectrometry, gas chromatography, and modified glassy or carbon electrode electrochemical methods will be considered, provided they show significant improvements and novelty compared to the established methods.