LC-MS/MS method development and validation of an antihistaminic, calcium channel blocker, di-phenyl-methyl-piperazine group containing cinnarizine in human plasma with an application to BA/BE studies in Indian volunteer

Antihistamine is drug which antagonises the action of histamine at the H1 receptors. Qualitatively all H1 antihistaminic have similar actions, but there are quantitative differences, especially in the sedative property. These drugs effectively block the histamine induced bronchoconstriction, contraction of intestinal and smooth muscle and triple response. It also suppressed the immediate or type-I hypersensitivity reaction but certain drugs are effective in preventing motion sickness. Cinnarizine is one of the drugs of antihistaminic medication. It is used to treat problems associated with the inner ear and the brain. The medicine is used to treat dizziness and sickness associated with motion sickness. This drug used in the treatment of vertigo and vestibular disorder and heart and blood vessel disorder. Cinnarizine inhibits the contractions of vascular smooth muscle cells by blocking L-type and T-type voltage gated calcium channel and it also binding to dopamine D2 receptor, histamine H1 receptor and muscarinic acetylcholine receptor. Cinnarizine contain diphenylmethylpiperazine group which protonated precursor ion was 369.3 and product ion 167.2 by using 0.1% formic acid in acetonitrile with 0.1% formic acid containing milli Q water added with 10.mM ammonium acetate as a binary flow. Internal standard precursor ion was 268.2 and product ion was 116.1 as a positive mode. The run time was very short 3.5 min and in between this run time 90% aqueous phase flow upto 0.9 min and 10% upto 2.50 min then again 90% flow upto 3.5 min. This method showed very low matrix effect which calculated matrix factor was 0.87 to 0.94 and recovery was very high 86.88% to 99.57%. So this method was very specific, selective, sensitive and reproducible which used for quantification of cinnarizine concentration of unknown Indian healthy human volunteers from their plasma.