Caslavska J, Hufschmid E, Theurillat R, Desiderio C, Wolfisberg H, Thormann W
Department of Clinical Pharmacology, University of Bern, Switzerland.
J Chromatogr B Biomed Appl. 1994 Jun 3;656(1):219-31. doi: 10.1016/0378-4347(94)00059-x.
Phenotypes for hydroxylation can be predicted by using mephenytoin and dextromethorphan as substrates, whereas phenotypes for acetylation can be determined with caffeine as probe drug. After single-dose administration of one of these drugs, of two of them simultaneously, or of the three drugs together, the major urinary metabolites (4-hydroxymephenytoin; dextrorphan, 3-methoxymorphinan, 3-hydroxymorphinan; 5-acetylamino-6-amino-3-methyluracil as decomposition product of 5-acetylamino-6-formylamino-3-methyluracil, 1-methylxanthine, respectively) of these substrates were analyzed by capillary electrophoretic techniques. No sample pretreatment other than enzymatic hydrolysis of the conjugated compounds was applied. Assays based on micellar electrokinetic capillary chromatography are shown to allow simultaneous and unambiguous phenotyping with mephenytoin and dextromethorphan or mephenytoin and caffeine. Simultaneous screening for all three polymorphisms with a single injection of a hydrolyzed urine is shown to be possible via use of multiwavelength absorption detection only. Phenotypes determined by electrokinetic capillary techniques are shown to agree with those obtained by analysis with customary assays based on high-performance liquid chromatography.
可以使用美芬妥英和右美沙芬作为底物来预测羟基化表型，而乙酰化表型则可以用咖啡因作为探针药物来确定。在单剂量给予这些药物中的一种、同时给予其中两种或三种药物一起后，通过毛细管电泳技术分析这些底物的主要尿代谢产物（4-羟基美芬妥英；右啡烷、3-甲氧基吗啡喃、3-羟基吗啡喃；分别作为5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶分解产物的5-乙酰氨基-6-氨基-3-甲基尿嘧啶、1-甲基黄嘌呤）。除了对结合物进行酶水解外，未进行其他样品预处理。基于胶束电动毛细管色谱的分析方法被证明可以同时且明确地对美芬妥英和右美沙芬或美芬妥英和咖啡因进行表型分析。仅通过使用多波长吸收检测，单次注射水解尿液就可以同时筛查所有三种多态性。通过电动毛细管技术确定的表型与通过基于高效液相色谱的常规分析方法获得的表型一致。
