人血清中反式曲马朵与反式氧去甲基曲马朵对映体的测定及其在治疗药物监测中的应用  被引量:1

Determination of the Enantiomers of (±) -Trans Tramadol and (±)-Trans O-demethyltramadol in Human Serum and Its Application in Therapeutic Drug Monitoring

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作  者:刘会臣[1] 杨燕燕[1] 王亚丽[1] 胡玉钦[1] 侯艳宁[1] 

机构地区:[1]白求恩国际和平医院,石家庄050082

出  处:《中国临床药理学杂志》2000年第5期377-380,共4页The Chinese Journal of Clinical Pharmacology

摘  要: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 determining the enantiomers of (±)-trans tramadol ((±)-trans T) and (±)-trans O-demethyltramadol ((±)-M1) in human serum, and to study the relationship between the clinical actions and the serum concentrations of the enantiomers of (±)-trans T and (±)-M1. METHODS: By using sulfobutylether-?-cyclodextrin as a chiral selector, a high performance capillary electrophoresis (HPCE) method was developed to analyze the enantiomers of (±)-trans T and (±)-M1. Twenty postoperative patients were divided into two groups and given multiple intravenous doses of (±)-trans T hydrochloride, 400 mg·d-1 or 300 mg·d-1. The relationship between the clinical actions and the serum concentrations of the enantiomers of (±)-trans T and (±)-M1was studied. RESULTS: The enantiomers of (±)-trans T and (±)-M1 in human serum were separated well. The linear ranges were 20~640 ?g·L-1 for the enantiomers of (±)-trans T, 10~160 ?g·L-1 for the enantiomers of (±)- M1. For the enantiomers of (±)-trans T and (±)-M1, the within-day and day-to-day RSDs were less than 10% and 15% respectively; the relative recoveries were from 92.30% to107.80%; the limit of detection was 1.10?g·L-1. The concentrations of the enantiomers of (±)-trans T, the frequency and serious level of adverse reactions were higher in 400 mg·d-1 group than that in 300 mg·d-1 group. The concentrations of the enantiomers of (±)- M1, and the analgesic effect were similar between the two groups. CONCLUSION: The HPCE method could be used in clinical therapeutic drug monitoring. There was close relationship between the analgesic effect and the concentration of (+)-M1 in serum. The frequency and serious level of adverse reactions might be attributed to the higher concentrations of the enantiomers of (±)-trans T, which may be due to the saturated metabolism.

关 键 词:药物监测 反式曲马朵 反式氧去甲基曲马朵对映体 药物不良反应 高效毛细管电泳 

分 类 号:R961[医药卫生—药理学] R971.1[医药卫生—药学]

 

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