Schwertner Harvey A, Kong Suk Bin
Clinical Research, Wilford Hall Medical Center, 2200 Bergquist Dr, Lackland AFB, TX 78236-5300, USA.
J Pharm Biomed Anal. 2005 Mar 9;37(3):475-9. doi: 10.1016/j.jpba.2004.11.014. Epub 2004 Dec 23.
Modafinil (Provigil) is a new wake-promoting drug that is being used for the management of excessive sleepiness in patients with narcolepsy. It has pharmacological properties similar to that of amphetamine, but without some of the side effects associated with amphetamine-like stimulants. Since modafinil has the potential to be abused, accurate drug-screening methods are needed for its analysis. In this study, we developed a high-performance liquid-chromatographic procedure (HPLC) for the quantitative analysis of modafinil in plasma and urine. (Phenylthio)acetic acid was used as an internal standard for the analysis of both plasma and urine. Modafinil was extracted from urine and plasma with ethyl acetate and ethyl acetate-acetic acid (100:1, v/v), respectively, and analyzed on a C18 reverse phase column with methanol-water-acetic acid (500:500:1, v/v) as the mobile phase. Recoveries from urine and plasma were 80.0 and 98.9%, respectively and the limit of quantitation was 0.1 microg/mL at 233 nm. Forty-eight 2-h post-dose urine samples from sham controls and from individuals taking 200 or 400 mg of modafinil were analyzed without knowledge of drug administration. All 16-placebo urine samples and all 32 2-h post-dose urine samples were correctly classified. The analytical procedure is accurate and reproducible and can be used for therapeutic drug monitoring, pharmacokinetic studies, and drug abuse screening.
莫达非尼（商品名：Provigil）是一种新型促醒药物，用于治疗发作性睡病患者的过度嗜睡。它具有与苯丙胺相似的药理特性，但没有一些与苯丙胺类兴奋剂相关的副作用。由于莫达非尼有被滥用的可能性，因此需要准确的药物筛选方法对其进行分析。在本研究中，我们开发了一种高效液相色谱法（HPLC）用于定量分析血浆和尿液中的莫达非尼。（苯硫基）乙酸用作血浆和尿液分析的内标。分别用乙酸乙酯和乙酸乙酯 - 乙酸（100:1，v/v）从尿液和血浆中提取莫达非尼，并在以甲醇 - 水 - 乙酸（500:500:1，v/v）为流动相的C18反相柱上进行分析。尿液和血浆的回收率分别为80.0%和98.9%，在233nm处的定量限为0.1μg/mL。在不知道给药情况的前提下，对来自假手术对照组以及服用200或400mg莫达非尼个体的48份给药后2小时的尿液样本进行了分析。所有16份安慰剂尿液样本以及所有32份给药后2小时的尿液样本均被正确分类。该分析方法准确且可重复，可用于治疗药物监测、药代动力学研究以及药物滥用筛查。
