Ding Ying, Huang Kai, Chen Lan, Yang Jie, Xu Wen-Yan, Xu Xue-Jiao, Duan Ru, Zhang Jing, He Qing
Drug Clinical Trial Institution, Wuxi People's Hospital, Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, People's Republic of China.
Biomed Chromatogr. 2014 Mar;28(3):446-52. doi: 10.1002/bmc.3054. Epub 2013 Nov 20.
A sensitive and accurate HPLC-MS/MS method was developed for the simultaneous determination of dextromethorphan, dextrorphan and chlorphenamine in human plasma. Three analytes were extracted from plasma by liquid-liquid extraction using ethyl acetate and separated on a Kromasil 60-5CN column (3 µm, 2.1 × 150 mm) with mobile phase of acetonitrile-water (containing 0.1% formic acid; 50:50, v/v) at a flow rate of 0.2 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The calibration curve was linear over the range of 0.01-5 ng/mL for dextromethorphan, 0.02-5 ng/mL for dextrorphan and 0.025-20 ng/mL for chlorphenamine. The lower limits of quantification for dextromethorphan, dextrorphan and chlorphenamine were 0.01, 0.02 and 0.025 ng/mL, respectively. The intra- and inter-day precisions were within 11% and accuracies were in the range of 92.9-102.5%. All analytes were proved to be stable during sample storage, preparation and analytic procedures. This method was first applied to the pharmacokinetic study in healthy Chinese volunteers after a single oral dose of the formulation containing dextromethorphan hydrobromide (18 mg) and chlorpheniramine malaeate (8 mg).
建立了一种灵敏、准确的HPLC-MS/MS方法，用于同时测定人血浆中的右美沙芬、右啡烷和氯苯那敏。采用乙酸乙酯液-液萃取法从血浆中提取三种分析物，并在Kromasil 60-5CN柱（3 µm，2.1×150 mm）上进行分离，流动相为乙腈-水（含0.1%甲酸；50:50，v/v），流速为0.2 mL/min。在三重四极杆串联质谱仪上采用正电喷雾电离，在多反应监测模式下进行定量分析。右美沙芬的校准曲线在0.01-5 ng/mL范围内呈线性，右啡烷在0.02-5 ng/mL范围内呈线性，氯苯那敏在0.025-20 ng/mL范围内呈线性。右美沙芬、右啡烷和氯苯那敏的定量下限分别为0.01、0.02和0.025 ng/mL。日内和日间精密度均在11%以内，准确度在92.9-102.5%范围内。所有分析物在样品储存、制备和分析过程中均被证明是稳定的。该方法首次应用于健康中国志愿者单次口服含氢溴酸右美沙芬（18 mg）和马来酸氯苯那敏（8 mg）制剂后的药代动力学研究。
