Ondansetron及其代謝物之血漿濃度測定及其在多劑量藥動學之應用   全文下載

Determination of Ondansetron and Metabolites in Plasma and its Pharmacokinetics in Cancer Patients

Ondansetron為5-HT3接受器之拮抗劑，在臨床上可用來治療因癌症化學療法、放射性療法及手術後所引發的噁心、嘔吐。本文報告一種簡單、敏感、精確的高效液相層析法，用來分析血漿中Ondansetron及其代謝物（7-hydroxy-ondansetron、8-hydroxy-ondansetron）的濃度，此分析方法是用CN管柱，以乙氰：0.0125 M pH4.7 醋酸氨緩衝液（2： 8, V／V）之混合溶液為移動相，並以UV305nm為檢測波長並使用傳統的溶劑萃取法處理血液樣品。結果顯示Ondansetron於20-800 ng／ml，二種代謝物於100-800 ng／ml的濃度範圍中，有很好的線性關係（r>0.999）及精確度（同日內和異日間的變異係數皆於10%左右），其最低可測得Ondansetron及2個代謝物濃度分別為5ng／ml、10 ng／ml及10 ng／ml。本法已成功地應用至臨床癌症病人Ondansetron多劑量藥動學之研究。"

Ondansetron is a novel 5-hydroxy-tryptamine3 (5-HT3)receptor antagonist which is a drug used clinically for chemotherapy-, radiotherapy-and postoperation induced nausea and emesis. A simple, sensitive, precise and accurate HPLC method for the detemination of ondansetron and its metabolites 7-hydroxy-ondansetron and 8-hydroxy-ondansetron in plasma is reported. Samples were prepared by a traditional, inexpensive solvent extraction method. The method employed a CN analytical column with an isocratic mobile phase of 20% acetonitrile in 80% 0.0125 M NH4OAc (pH = 4.7) and ultraviolet detection at 305 nm. Using this method, the calibration curves of ondansetron, 7-hydroxy-ondansetron and 8-hydroxy-ondansetron in plasma in the range of interest (20-800 ng/ml, 100-800 ng/ml and 100-1000 ng/ml, respectively) showed good linearity (r >0.999) and precision(both between-day and within-day coefficients of variation less or around 10%). The lower detection limits of this assay method for ondansetron and its 7-OH and 8-OH metabolites were 5 ng/ml, 10 ng/ml and 10 ng/ml respectively. This method has been successfully applied to the pharmacokinetic study of ondansetron in cancer patients receiving single i. v. infusion followed by a multiple oral dose of ondansetron.