王小桐,金艺,邵楠,蒋唤,徐海燕
WANG Xiaotong,JIN Yi,SHAO Nan,JIANG Huan,XU Haiyan

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的建立大鼠血浆中20(R/S)-25-OH-PPD差向异构体的LC-MS/MS法,并研究20(R/S)-25-OH-PPD在大鼠体内立体选择性药代动力学行为。方法色谱柱:Shiseido C18(150 mm×4.6 mm,5μm),以乙腈-5 mmol·L-1醋酸铵缓冲溶液(体积比为73∶27)为流动相,等度洗脱方式进行分离,样品经沉淀蛋白法处理后进行分析。结果 20(R)和20(S)构型在5.0~2000μg·L-1质量浓度内线性关系良好;日内和日间精密度(CV)不大于6.2%;大鼠血浆中20(R)-25-OH-PPD和20(S)-25-OH-PPD的提取回收率分别在78.3%~85.2%和81.6%~86.8%内,基质效应分别在103.3%~105.9%和100.6%~107.2%内。大鼠静注或灌胃分别给予25-OH-PPD差向异构体后,血浆中S构型的浓度明显高于R构型,S构型半衰期明显长于R构型,R、S构型间未见相互转化。结论本方法可用于同时测定20(R/S)-25-OH-PPD,并成功应用于25-OH-PPD差向异构体在大鼠体内的立体选择性药代动力学研究。
Objective A liquid chromatography tandem mass spectrometry( LC-M S/M S) method w as developed for simultaneous determination of 20( R/S)-25-OH-PPD epimers. The validated method w as applied for the stereoselective pharmacokinetic study of 20( R/S)-25-OH-PPD epimers in rats after intravenous and oral administration. Methods After protein precipitation,the analyte and internal standard w ere separated on a Shiseido C18( 150 mm × 4. 6 mm,5 μm) by the gradient elution with acetoritrile-5 mmol·L-1 ammonium acetate( V ∶ V = 73∶ 27) as mobile phase. Results The method show ed good linearity in the range of 5. 0-2000 μg·L-1 for both epimers. The intra-and inter-assay precision w ere less than 6.2%. The extraction recovery w as 78. 3%-85. 2% for 20( R)-epimer and 81. 6%-86. 8% for 20( S)-epimer.The matrix effects of 20( R) and 20( S) epimers w ere 103. 3%-105. 9% and 100. 6%-107. 2%,respectively.After rats w ere intravenously or orally given 25-OH-PPD epimers,S-epimer exhibited significantly higher plasma levels and slow er elimination rate than R-epimer. Conclusions The method is successfully applied for the stereoselective pharmacokinetic investigation of 20( R/S)-25-OH-PPD epimers in rats.

关键词(KeyWords)： 25-OH-PPD;LC-MS/MS;立体选择性;药代动力学
25-OH-PPD;LC-MS/MS;stereoselective;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 辽宁省科学技术基金资助项目(2015020563)

作者(Author): 王小桐,金艺,邵楠,蒋唤,徐海燕
WANG Xiaotong,JIN Yi,SHAO Nan,JIANG Huan,XU Haiyan

DOI: 10.14066/j.cnki.cn21-1349/r.2018.04.006

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