Morphine radioimmunoassay specificity before and after extraction of plasma and cerebrospinal fluid.
Morphine radioimmunoassay specificity before and after extraction of plasma and cerebrospinal fluid.
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血浆和脑脊液提取前后吗啡放射免疫测定的特异性。
DOI：
10.1002/jps.2600720107
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发表时间：
1983
影响因子：
3.8
通讯作者：
Houde,RW
中科院分区：
文献类型：
--
作者：
Grabinski,PY;Kaiko,RF;Walsh,TD;Foley,KM;Houde,RW
现有的吗啡放射免疫分析方法使用的是3-O-羧甲基吗啡的抗血清，由于交叉反应代谢物的血浆浓度相对较高，因此对于重复口服后的临床药代动力学研究缺乏足够的特异性。描述了一种回收药物和去除其极性代谢物的程序。一步溶剂萃取法对吗啡的回收率为97%(CV6.9%)，未发现主要的非活性代谢物吗啡-3-葡萄糖醛酸苷。提取和未提取的吗啡放射免疫分析标准曲线具有相似的斜率、精密度和I50值。提取前的放射免疫分析消除了吗啡-3-葡萄糖醛酸苷与抗血清的交叉反应。在没有预先提取的情况下，重复口服吗啡后的表观血浆吗啡浓度依赖于稀释度。相反，当放射免疫分析之前提取时，浓度是独立于稀释的。23例癌症患者用药后4小时血浆吗啡浓度为26 ng/ml(95%可信区间，20-33 ng/ml)，而不用药的表观浓度为80 ng/ml(95%可信区间，-96 ng/ml)。这些数据表明，通过结合预先提取和放射免疫分析，可以在重复口服剂量后获得特定的、稳定的血浆吗啡水平。然而，在接受单次静脉注射的四名患者的脑室脑脊液中，提取的和未提取的吗啡浓度之间没有显著差异。在放射免疫分析之前，提取程序提供了在含有相对较高浓度的交叉反应代谢物的生物液中测量吗啡所需的特异性。
Currently available morphine radioimmunoassays, using antiserum to 3‐O‐carboxymethylmorphine, lack sufficient specificity for clinical pharmacokinetic studies following repeated oral doses due to the relatively high plasma concentrations of cross‐reacting metabolites. A procedure is described for the recovery of the drug and removal of its polar metabolites. The single‐step solvent extraction recovered 97% (CV6.9%) morphine and none of the major inactive metabolite, morphine‐3‐glucuronide. Extracted and nonextracted morphine radioimmunoassay standard curves had comparable slopes, precision, and I50values. Cross reactivity between morphine‐3‐glucuronide and the antiserum was eliminated when the radioimmunoassay was preceded by extraction. Without prior extraction, the apparent plasma morphine concentration following repeated oral doses was dilution dependent. In contrast, concentration was dilution independent when the radioimmunoassay was preceded by extraction. The plasma morphine concentration in 23 cancer patients at 4 hr following their previous dose (calculated to 10 mg of base) was 26 ng/ml (95% confidence interval (CI), 20–33 ng/ml) with prior extraction, as compared with the apparent concentration of 80 ng/ml (95% CI, 64–96 ng/ml) without extraction. These data indicate that by combining prior extraction with radioimmunoassay, specific, steady‐state plasma morphine levels can be obtained following repeated oral doses. However, no significant differences were observed between extracted and nonextracted morphine concentrations in ventricular cerebrospinal fluid from four patients who had received a single intravenous dose. The extraction procedure, prior to radioimmunoassay, provides the specificity required for the measurement of morphine in biofluids that contain relatively high concentrations of cross‐reacting metabolites.