【摘要】：目的建立同時測定大鼠血漿中曲馬多、O-去甲基曲馬多、N-去甲基曲馬多、N,O-二去甲基曲馬多和異丙嗪的UPLC-MS方法,并將其應用于復方鹽酸曲馬多和鹽酸異丙嗪注射液在大鼠體內的藥動學研究。方法采用沉淀蛋白法進行樣品預處理,色譜柱為Acquity UPLC BEH C18(50 mm×2.1 mm,1.7μm)柱,流動相采用乙腈-5 mmol·L~(-1)醋酸銨(含體積分數(shù)0.02%甲酸溶液)梯度洗脫,以正離子選擇離子監(jiān)測模式進行檢測。結果血漿中曲馬多、O-去甲基曲馬多、N-去甲基曲馬多、N,O-二去甲基曲馬多和異丙嗪分別在質量濃度為1.84~368.0μg·L~(-1)、0.21~42.00μg·L~(-1)、0.49~98.00μg·L~(-1)、0.48~96.00μg·L~(-1)和1.90~380.0μg·L~(-1)內線性關系良好,日內和日間精密度RSD均不超過10.8%,提取回收率為93.2%~109.5%,基質效應為93.3%~104.6%,5個分析物的血漿樣品在所考察的儲存條件下均可保持穩(wěn)定。結論該方法適用于復方鹽酸曲馬多和鹽酸異丙嗪注射液在大鼠體內的藥動學研究。與單獨給藥后的藥動學行為進行比較,復方同時給藥后,曲馬多及其3個代謝物的ρmax和AUC均增加,特別是在雌性大鼠體內;而復方給藥后,曲馬多對異丙嗪的藥動學行為無明顯影響。
[Abstract]:Objective to establish a UPLC-MS method for the simultaneous determination of tramadol, O-demethyltramadol, N-demethyltramadol, N, O-didemethyltramadol and promethazine in rat plasma. It was applied to the pharmacokinetics of compound tramadol hydrochloric acid and promethazine Hydrochloride injection in rats. Methods the sample was pretreated by precipitation protein method. The chromatographic column was Acquity UPLC BEH C18 (50 mm 脳 2.1 mm, 1.7 渭 m). The mobile phase was eluted with acetonitrile-5 mmol 路L ~ (- 1) ammonium acetate (containing 0.02% formic acid solution). The positive ion selective ion monitoring mode was used for detection. Results the concentrations of tramadol, O-demethyltramadol, N-demethyltramadol, N, O-didemethyltramadol and promethazine in plasma were 1.84 ~ 368.0 渭 g 路L ~ (- 1) and 0.21 ~ 42.00 渭 g 路L ~ (- 1), respectively. There is a good linear relationship between 0.49 ~ 98.00 渭 g 路L ~ (- 1), 0.48 ~ 96.00 渭 g 路L ~ (- 1) and 1.90 ~ 380.0 渭 g 路L ~ (- 1). The intra-day and inter-day precision RSD is less than 10.8%, and the recovery is 93.2% 鈮，

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