高效液相色谱法同时测定人血浆中卡马西平、奥卡西平及其活性代谢产物的浓度和临床应用

目的：建立同时测定人血浆中卡马西平（CBZ）、10,11-环氧卡马西平（CBZE）、奥卡西平（OXC）和单羟基卡马西平（MHD）浓度的高效液相色谱法,并将其应用于临床中卡马西平、奥卡西平及其活性代谢产物血药浓度的测定。方法：以苯巴比妥为内标,血浆经乙醚-二氯甲烷（2∶1）提取。色谱柱为WondaSil C₁₈柱（150 mm×4.6 mm,5 μm）,流动相为甲醇∶水=50∶50,柱温30℃,流速1.0 mL·min^-1,检测波长215 nm,进样量20 μL。结果：卡马西平、10,11－环氧卡马西平、奥卡西平和单羟基卡马西平标准曲线范围分别为0.1~20,0.05~10,0.05~20,0.2~50 mg·L^-1,最低检测限分别为0.1,0.05,0.05,0.2 mg·L^-1,日内、日间精密度均小于10%。结论：该方法灵敏准确,简便快速,适用于卡马西平、奥卡西平及其代谢产物血药浓度检测。     

Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites

We developed a gas chromatography isotope-dilution high-resolution mass spectrometry (GC/ID-HRMS) method for measuring 14 polycyclic aromatic hydrocarbon (PAH) metabolites representing seven parent PAHs in 3 mL of urine at low parts-per-trillion levels. PAH levels were determined in urine samples collected in 1999 and 2000 from approximately 2400 participants in the National Health and Nutrition Examination Survey, and, for the first time, reference range values were calculated for these metabolites in the US population. Using this GC/ID-HRMS method, we found detectable concentrations for monohydroxy metabolite isomers of fluorene, phenanthrene, fluoranthene, pyrene, and chrysene, benzo[c]phenanthrene, and benz[a]anthracene. Some monohydroxy metabolite isomers of benzo[c]phenanthrene, chrysene, and benz[a]anthracene exhibited low detection frequencies that did not allow for geometric mean calculations. Our study results enabled us to establish a reference range for the targeted PAHs in the general US population.     

Contact dermatitis from polyfunctional acrylic monomers.

Five out of 26 men employed formulating radiation drying printing ink developed eczematous dermatitis. Positive patch tests were obtained with two polyfunctional acrylic monomers, pentaerythritol triacrylate and trimethylol propane triacrylate and with formulations containing these in four affected employees. Cross sensitization was observed to dipentaerythritol monohydroxy pentaacrylate in each case. A fifth employee appeared to have developed irritant dermatitis from contact with these materials.     

反相-高效液相色谱法测定奥卡西平活性代谢物及其在健康人体的药代动力学特征

目的建立测定奥卡西平活性代谢物的高效液相色谱法并进行药代动力学研究。方法10名健康志愿者单剂量口服奥卡西平300mg;血浆样品经液-液萃取,用高效液相色谱法检测奥卡西平10-单羟基代谢物(MHD)。用3P87程序进行数据处理。结果此方法适于血浆MHD浓度的检测。单剂量口服奥卡西平后,MHD的血浆浓度符合一级吸收的一室模型;其主要药代动力学参数为:tmax=(4.10±0.79)h,Cmax=(4.64±0.53)mg·L-1,t1/2ke=(15.05±2.32)h,AUC0-48=(112.97±14.25)mg·h·L-1。结论该法能高效、灵敏、准确地测定血浆中MHD。     

HPLC法测定人血浆中奥卡西平活性代谢产物单羟基卡马西平的浓度

目的建立HPLC法测定奥卡西平活性代谢产物单羟基卡马西平的血药浓度。方法血浆样品经甲醇处理后,以奥硝唑为内标,采用HPLC法测定,其中,色谱柱为ZORBAX Eclipse XDB-C18(150 mm×4.6 mm,5μm),流动相为水-乙腈(80∶20,V/V),流速1.0 ml/min,柱温35℃,双波长检测:192 nm检测单羟基卡马西平,318 nm检测奥硝唑。结果单羟基卡马西平血药浓度在2~50μg/ml(r=0.9986)范围内线性关系良好,定量下限浓度为2μg/ml;准确度在95.57%~100.59%之间,日内、日间精密度RSD均小于15%;单羟基卡马西平及内标的平均提取回收率在89.62%~98.76%之间;稳定性的RSD均小于6%。结论该方法专属性强、灵敏度高,且操作简便,可用于单羟基卡马西平血药浓度的临床检测。     

THE DISTRIBUTION OF 10-HYDROXY CARBAZEPINE IN BLOOD COMPARTMENTS

The distribution of 10-hydroxy carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), was investigated in plasma and red cells. After the oral administration of 600 mg of OXC to nine healthy volunteers, blood samples were withdrawn for the next 56 h and packed red cells were separated from plasma by centrifugation. Also, in vitro studies of plasma binding of MHD were carried out by a dialysis technique. Results showed that the in vitro protein binding was low. The mean bound concentration ranged from 37 to 40%; however, an affinity of MHD to red corpuscles was found. These observations indicate that MHD red blood cell concentrations together with plasma measurements could be useful in cases of inefficacy or toxicity in order to make the appropriate drug adjustments. © 1997 by John Wiley & Sons, Ltd.