本文選題：孕三烯酮(三烯高諾酮) + 液相色譜-質(zhì)譜聯(lián)用��； 參考：《藥物分析雜志》2017年07期

【摘要】：目的:建立快速靈敏的HPLC-MS/MS法測(cè)定巴馬小型豬血漿中孕三烯酮的濃度,并研究孕三烯酮膠囊在巴馬小型豬體內(nèi)的藥代動(dòng)力學(xué)特征。方法:以巴馬小型豬為實(shí)驗(yàn)動(dòng)物,連續(xù)給藥12周,每周給藥2次,于給藥后不同時(shí)間點(diǎn)采集血樣。通過測(cè)定多次給藥后小型豬血漿中孕三烯酮的濃度,計(jì)算其藥代動(dòng)力學(xué)參數(shù)。測(cè)定血漿樣品以孕二烯酮為內(nèi)標(biāo),經(jīng)環(huán)己烷液液萃取后進(jìn)行LC-MS/MS分析。色譜柱:Agilent ZORBAX Extend-C_(18)(2.1 mm×50 mm,5μm);流動(dòng)相:水(含0.1%甲酸)-乙腈(含0.1%甲酸),梯度洗脫;流速:0.40 m L·min~(-1);進(jìn)樣量:20μL;柱溫:35℃。質(zhì)譜檢測(cè)采用ESI正離子模式,掃描方式為多重反應(yīng)監(jiān)測(cè)(MRM)模式,選擇檢測(cè)離子反應(yīng)對(duì)為m/z 309.2→241.1(孕三烯酮),m/z 311.2→109.1(孕二烯酮)。結(jié)果:孕三烯酮在0.1~10 ng·mL~(-1)濃度范圍內(nèi)線性良好(r=0.999 9),定量下限為0.1 ng·mL~(-1)。提取回收率均高于83.1%,日間、日內(nèi)RSD均小于11.3%,專屬性良好,在本實(shí)驗(yàn)涉及的條件下樣品穩(wěn)定。8只小型豬首次給藥后C_(max)為(2.85±0.96)μg·L~(-1),T_(max)為(2.06±0.62)h,t_(1/2)為(8.43±4.13)h,AUC_(0-85)為(23.81±8.62)μg·L·h~(-1),AUC_(0-∞)為(24.36±8.73)μg·L·h~(-1),MRT_(0-85)為(8.40±2.44)h,MRT_(0-∞)為(9.81±3.88)h;末次給藥后C_(max)為(2.70±0.55)μg·L~(-1),T_(max)為(1.69±0.65)h,t_(1/2)為(8.51±3.72)h,AUC_(0-85)為(17.71±4.89)μg·L·h~(-1),AUC_(0-∞)為(18.51±4.48)μg·L·h~(-1),MRT_(0-85)為(8.54±3.50)h,MRT_(0-∞)為(9.98±4.41)h。結(jié)論:該方法準(zhǔn)確、快速、靈敏,專屬性強(qiáng),適用于動(dòng)物實(shí)驗(yàn)及臨床上測(cè)定血漿中孕三烯酮的濃度及其藥代動(dòng)力學(xué)研究。多次給予孕三烯酮膠囊后2 h血藥濃度相差不大,且用藥后無不良反應(yīng),安全性較高。
[Abstract]:Aim: to establish a rapid and sensitive HPLC-MS / MS method for the determination of pregnenone in plasma of Bama miniature pigs and to study the pharmacokinetics of pregnenone capsules in Bama miniature pigs. Methods: Bama miniature pigs were used as experimental animals for 12 weeks, twice a week. Blood samples were collected at different time points after administration. The pharmacokinetic parameters were calculated by determining the concentration of pregnenone in plasma of miniature pigs after repeated administration. The plasma samples were analyzed by LC-MS / MS after extraction of cyclohexane liquid with pregnenone as internal standard. The mobile phase consisted of water (0.1% formic acid) -acetonitrile (0.1% formic acid) and acetonitrile (0.1% formic acid), gradient elution; flow rate: 0.40 mL 路min ~ (-1); injection volume: 20 渭 L; column temperature: 35 鈩，

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