LC-MS/MS method for the quantification of carbinoxamine in human plasma

Abstract

A simple, reverse-phase high performance liquid chromatographic method with mass spectrometric detection (HPLC-MS/MS) was developed for determination of carbinoxamine in human plasma using pargeverine HCl as an internal standard. The procedure involves a simple protein precipitation technique using BDS HYPERSIL C8 (100 x 4.6mm) column. The mobile phase used was acetonitrile: buffer (25mm ammonium formate solution) (80:20). Precipitation was done using acetonitrile and detection was done in MRM mode, using an Electro Spray positive ionization. The ion transition monitored was (m/z) carbinoxamine (Q1 Mass: 291.2; Q3 Mass: 167.1), Internal standard (Q1 Mass: 338.1; Q3 Mass; 167.0). The retention time of carbinoxamine and internal Standard were 1.61 and 1.75 respectively. Method was evaluated in terms of linearity, accuracy, precision, recovery, sensitivity. The simple extraction procedure and short chromatographic runtime make the method suitable for therapeutic drug monitoring studies. I. Introduction Carbinoxamine (CX) (2-((4-chlorophenyl)-pyridin-2-yl-methoxy)-N, N-dimethyl-ethanamine) (Fig. 1) is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It is also used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as docromolyn and nedocromil, carbinoxamine competes with free histamine for binding at HA-receptor sites. Carbinoxamine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than other antihistamines, which probably accounts for the antidyskinetic action of carbinoxamine.