人血浆中O-去甲右美沙芬的测定及药代动力学研究  

Determination of dextrorphan in human plasma and pharmacokinetic study

作　　者：刘丹[1] 陈笑艳[1] 张逸凡[1] 钟大放[1] 顾琦[1] 张勇[1] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室,辽宁沈阳110016

出　　处：《药学学报》2004年第6期449-452,共4页Acta Pharmaceutica Sinica

摘　　要：目的　建立直接测定人血浆中O 去甲右美沙芬的方法 ,并应用于药代动力学研究。方法　 1 8名健康受试者单剂量po氢溴酸右美沙芬 6 0mg后 ,血浆样品经液 液萃取 ,通过液相色谱 质谱 质谱联用法测定其活性代谢物O 去甲右美沙芬的浓度 ,用非室模型计算药代动力学参数。结果　O 去甲右美沙芬测定的线性范围为 0 2～ 80μg·L- 1 ;其主要药代动力学参数Tmax 为 (2 1± 0 7)h ,Cmax为 (1 4± 8) μg·L- 1 ,T1 2 为 (3 8± 1 8)h ,用梯形法计算 ,AUC0 -t为 (6 0± 37) μg·h·L- 1 。结论　该法灵敏度高 ,操作简便 ,可直接测定活性代谢物 。Aim To develop a sensitive and specific LC/MS/MS method for direct determination of dextrorphan in human plasma and to study the pharmacokinetics of dextrorphan. Methods After a single oral dose of 60 mg dextromethorphan hydrobromide to 18 healthy Chinese male volunteers, the plasma concentration of dextrorphan, an active metabolite of dextromethorphan, was determined. Dextrorphan and internal standard chlorpheniramine were extracted from plasma using liquid liquid extraction, then separated on a Zorbax Extend C 18 column. The mobile phase consisted of methanol water formic acid (70∶30∶1), at a flow rate of 0 5 mL·min -1 . A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor to product ion combinations of m/z 258 to 157 and m/z 275 to 230 was performed to quantify dextrorphan. The pharmacokinetic parameters of dextrorphan were calculated by non compartment model statistics. Results The linear calibration curves were obtained in the concentration range of 0 2-80 μg·L -1 . Each plasma sample was chromatographed within 3 0 min. The intra and inter day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 8%. Accuracy determined at three concentrations (0 5, 6 0 and 70 μg·L -1 for dextrorphan) ranged from 98 8% to 100 6%. Pharmacokinetic parameters of dextrorphan was obtained as follows: T max was (2 1±0 7) h, C max was (14±8) μg·L -1 , T 1/2 was (3 8±1 8) h, AUC 0-t was (60±37) μg·h·L -1 . Conclusion Plasma concentration of the active metablite dextrorphan was directly determined. The method is sensitive and convenient, and is proved to be suitable for clinical investigation of dextrorphan pharmacokinetics and bioequivalence evaluation of formulations containing dextromethorphan.

关 键 词：血药浓度 O-去甲右美沙芬 测定 药代动力学 液相色谱-质谱-质谱联用法 

分 类 号：R969.1[医药卫生—药理学]