European Journal of Biomedical and Pharmaceutical Sciences

DETERMINATION AND QUANTIFICATION OF A N-NITROSO-N-METHYLCYCLOHEXYLAMINE IN THE BROMHEXINE HYDROCHLORIDE ACTIVE PHARMACEUTICAL INGREDIENT BY GC-MS/MS

Vinayak T. Vele*, Kishor More, Mohan A. Chandavarkar and Krupali Shah

ABSTRACT

A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was developed for the quantification of N-nitroso-N-methylcyclohexylamine in the Bromhexine Hydrochloride active pharmaceutical ingredient. Chromatographic separation was achieved using a DB-1MS column, with Helium as carrier gas at a 2.5 ml/ min flow rate. Quantification of impurity was carried out using triple quadrupole mass detection with electrospray ionization in the multiple reaction monitoring mode. The method was validated with good linearity over the concentration range of 0.037-0.562 ppm for N-nitroso-N-methylcyclohexylamine. The correlation coefficient obtained in each case was >0.9960. The recoveries were found to be satisfactory over the range between 80.0 and 120.0 % for N-nitroso-N-methylcyclohexylamine. The developed method was able to quantitate N-nitroso-N-methylcyclohexylamine at a concentration level of 3.75 ng mL-l (0.00375 ppm with respect to 10 mg mL-1 Bromhexine Hydrochloride).

Keywords: Nitrosamine, N-nitroso-N-methylcyclohexylamine, GCMS/MS, Validation, Bromhexine Hydrochloride.