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目的:建立人血清中反式曲马朵((±)-trans T)与氧去甲基曲马朵((±)-M1)对映体的测定方法,研究血清中 (±)-trans T和(±)-M1对映体浓度与临床效果的关系。方法:以磺丁基-β-环糊精为手性选择剂,高效毛细管电泳(HPCE)法测定人血清中(±)-trans T与(±)-M1对映体的浓度;监测20例术后病人静滴盐酸(±)-trans T 400 mg·d-1 或 300 mg·d-1后血清中 (±)-trans T与 (±)-M1对映体浓度,并观察临床镇痛效果及药物不良反应。结果:血清中 (±)-trans T与 (±)-M1对映体分离效果良好,(±)-trans T与 (±)-M1对映体的线性范围分别为20~640 ?g·L-1 和10~160?g·L-1,相对回收率在92.30%~107.80%之间,日内RSD小于10%,日间RSD小于15%,最低检测浓度为1.10?g·L-1。400 mg·d-1 组病人血清中(±)-trans T对映体的浓度、药物不良反应的发生率和严重程度明显高于300 mg·d-1 组病人,而400 mg·d-1组和300 mg·d-1组病人血清中(±)-M1对映体浓度及镇痛效果无明显区别。结论:所建立的HPCE方法可用于临床治疗药物监测。血清中(+)-M1的浓度与镇痛效果密切相关,(±)-trans T对映体浓度过高可能是药物不良反应的发生率增高和程度增强的原因之一。
OBJECTIVE: To establish a method for the determination of (±) -trans T and (±) -M1 enantiomers in human serum and to study the effect of (±) -trans T And (±) -M1 enantiomer concentrations and clinical outcomes. Methods: The concentrations of (±) -trans T and (±) -M1 enantiomers in human serum were determined by high performance capillary electrophoresis (HPCE) with sulfobutyl-β-cyclodextrin as chiral selector. The serum concentrations of (±) -trans T and (±) -M1 enantiomers in the patients after intravenous infusion of (±) -trans T 400 mg · d-1 or 300 mg · d-1 after operation were measured and the clinical analgesia Effects and Adverse Drug Reactions. Results: (±) -trans T was separated from (±) -M1 enantiomers in serum, and the linear ranges of (±) -trans T and (±) -M1 enantiomers were 20 ~ 640 μg · L The relative recoveries ranged from 92.30% to 107.80%. The RSD was less than 10% in the day, the RSD was less than 15%, and the lowest concentration was 1.10 μg · L-1. The concentration of (±) -trans T enantiomer in the serum of 400 mg · d-1 group was significantly higher than that in the 300 mg · d-1 group, and the incidence of adverse drug reactions was 400 mg · d-1 Group and 300 mg · d-1 group of serum (±) -M1 enantiomer concentration and analgesic effect no significant difference. Conclusion: The established HPCE method can be used for clinical treatment of drug monitoring. The concentration of (+) - M1 in serum is closely related to the analgesic effect. The high concentration of (±) -trans T enantiomer may be one of the reasons for the increased incidence and degree of adverse drug reactions.