Determination of unlabeled and 13C6-labeled moricizine in human plasma using thermospray liquid chromatography-mass spectrometry

Moricizine hydrochloride is an orally effective antiarrhythmic agent currently marketed in the Soviet Union and undergoing clinical testing in the United States. To facilitate the simultaneous analysis of unlabeled and 13C6-labeled moricizine in human plasma, a specific and sensitive method employing liquid-liquid extraction followed by thermospray liquid chromatography-mass spectrometry (LC-MS) was developed. Plasma samples, after addition of [2H11]moricizine as an internal standard, were extracted into methylene chloride under alkaline conditions. Extracts were evaporated, reconstituted with mobile phase, and chromatographed on an ODS column. The LC mobile phase consisted of methanol-0.1 M ammonium acetate containing 0.2% triethylamine (65:35) and it was used at a flow-rate of 1.5 ml/min. Under these conditions, moricizine and [13C6]moricizine coeluted at 1.2 min, while [2H11]moricizine eluted slightly earlier. The MS system consisted of a Finnigan 4600 TSQ and a Vestec thermospray interface. Selected ions at m/z 428, 434, and 439 were scanned at 0.2 s per ion. Over a plasma concentration range of 10-800 ng/ml, intra-day precision (n = 3) ranged from 1.8 to 13.3% and intra-day accuracy ranged from 1.9 to 15.8%. This method was successfully used to assay human plasma samples from a pilot moricizine bioavailability study in which tablets and solution containing moricizine hydrochloride and [13C6]moricizine, respectively, were simultaneously administered.