【摘要】：目的建立同時(shí)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(yīng)用于復(fù)方鹽酸曲馬多和鹽酸異丙嗪注射液在大鼠體內(nèi)的藥動(dòng)學(xué)研究。方法采用沉淀蛋白法進(jìn)行樣品預(yù)處理,色譜柱為Acquity UPLC BEH C18(50 mm×2.1 mm,1.7μm)柱,流動(dòng)相采用乙腈-5 mmol·L~(-1)醋酸銨(含體積分?jǐn)?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(jìn)行檢測。結(jié)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(zhì)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(nèi)線性關(guān)系良好,日內(nèi)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(zhì)效應(yīng)為93.3%~104.6%,5個(gè)分析物的血漿樣品在所考察的儲(chǔ)存條件下均可保持穩(wěn)定。結(jié)論該方法適用于復(fù)方鹽酸曲馬多和鹽酸異丙嗪注射液在大鼠體內(nèi)的藥動(dòng)學(xué)研究。與單獨(dú)給藥后的藥動(dòng)學(xué)行為進(jìn)行比較,復(fù)方同時(shí)給藥后,曲馬多及其3個(gè)代謝物的ρmax和AUC均增加,特別是在雌性大鼠體內(nèi);而復(fù)方給藥后,曲馬多對(duì)異丙嗪的藥動(dòng)學(xué)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，

本文編號(hào)：2475964