超高效液相色谱-串联质谱同时检测大鼠血浆中羟基安非他酮、羟基美托洛尔、1-羟基咪达唑仑、对乙酰氨基酚和羟基甲苯磺丁脲
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摘要
目的以地西泮为内标,使用超高效液相色谱-串联质谱(UPLC-MS/MS)同时测定大鼠血浆中羟基安非他酮、羟基美托洛尔、1-羟基咪达唑仑、对乙酰氨基酚和羟基甲苯磺丁脲。方法血浆样品用乙腈沉淀法去除蛋白,色谱分离采用UPLC BEHC_(18)(2.1 mm×50 mm,1.7μm)柱,流动相为乙腈-水(含0.1%甲酸)梯度洗脱,采用电喷雾多反应监测模式定量。结果日间和日内精密度<13%,准确度为94.5%～107.2%,提取回收率在83.2%～92.6%。血浆标准曲线在1 ng/ml～1 000 ng/ml浓度内呈线性,相关系数(r)>0.997。结论该方法可用于5种CYP450亚型探针药物给药后的代谢产物药代动力学研究。
Objective A specific ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method has been developed for the simultaneous determination of hydroxyburpropion, hydroxymetoprolol, 1-hydroxymidazolam, acteminophen and hydroxytolbutamide in rat plasma, with diazepam as internal standard. Methods Plasma samples were protein precipitated with acetonitrile. Chromatographic separation was achieved using a UPLC BEHC_(18) column(2.1 mm×50 mm, 1.7 μm). The mobile phase was consisted of acetonitrile and water(containing 0.1% formic acid) for gradient elution. The triple quadrupole mass spectrometric detection was operated by multiple reactions monitoring in positive electrospray ionization. Results The day and inday precisions were less than 13%, and the accuracy ranged from 94.5% to 107.2%. The extraction efficiency was within 83.2%-92.6%. The calibration curves in plasma were linear within 1 ng/ml-1 000 ng/ml, with correlation coefficient(r) greater than 0.997. Conclusion This method can be used for pharmacokinetic studies of metabolites in five CYP450 subtype after probe drug administration.
Objective A specific ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method has been developed for the simultaneous determination of hydroxyburpropion, hydroxymetoprolol, 1-hydroxymidazolam, acteminophen and hydroxytolbutamide in rat plasma, with diazepam as internal standard. Methods Plasma samples were protein precipitated with acetonitrile. Chromatographic separation was achieved using a UPLC BEHC_(18) column(2.1 mm×50 mm, 1.7 μm). The mobile phase was consisted of acetonitrile and water(containing 0.1% formic acid) for gradient elution. The triple quadrupole mass spectrometric detection was operated by multiple reactions monitoring in positive electrospray ionization. Results The day and inday precisions were less than 13%, and the accuracy ranged from 94.5% to 107.2%. The extraction efficiency was within 83.2%-92.6%. The calibration curves in plasma were linear within 1 ng/ml-1 000 ng/ml, with correlation coefficient(r) greater than 0.997. Conclusion This method can be used for pharmacokinetic studies of metabolites in five CYP450 subtype after probe drug administration.
引文
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[10] Wen C, Cai J, Lin C, et al. Gradient elution liquid chromatography mass spectrometry determination of acetylcorynoline in rat plasma and its application to a pharmacokinetic study[J]. Xenobiotica, 2014, 44(8): 743-748.
[11] Ma J, Ding X, Sun C, et al. Development and validation a liquid chromatography mass spectrometry for determination of solasodine in rat plasma and its application to a pharmacokinetic study[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2014, 963: 24-28.
[12] Logan BK, Yeakel JK, Goldfogel G, et al. Dextromethorphan abuse leading to assault, suicide, or homicide[J]. J Forensic Sci, 2012, 57(5): 1388-1394.
[13] Miller SC. Dextromethorphan to dextrorphan: a pathway towards abuse liability[J]. Hum Psychopharmacol, 2011, 26(1): 89-90, author reply 91.
[14] Cai J, Dai DP, Geng PW, et al. Effects of 22 novel CYP2D6 variants found in the Chinese population on the bufuralol and dextromethorphan metabolisms in vitro[J]. Basic Clin Pharmacol Toxicol, 2016, 118(3): 190-199.
[15] Shin EJ, Lee PH, Kim HJ, et al. Neuropsychotoxicity of abused drugs: Potential of dextromethorphan and novel neuroprotective analogs of dextromethorphan with improved safety profiles in terms of abuse and neuroprotective effects[J]. J Pharmacol Sci, 2008, 106(1): 22-27.
[2] Tan ML, Lim LE. The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms′ activities, a review of possible herb-drug interaction risks[J]. Drug Chem Toxicol, 2015, 38(3): 241-253.
[3] Qin CZ, Ren X, Tan ZR, et al. A high-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry[J]. Biomed Chromatogr, 2014, 28(2): 197-203.
[4] Liu LY, Han YL, Zhu JH, et al. A sensitive and high-throughput LC-MS/MS method for inhibition assay of seven major cytochrome P450s in human liver microsomes using an in vitro cocktail of probe substrates[J]. Biomed Chromatogr, 2015, 29(3): 437-444.
[5] de Andrés F, LLerena A. Simultaneous determination of cytochrome P450 oxidation capacity in humans: A review on the phenotyping cocktail approach[J]. Curr Pharm Biotechnol, 2016, 17(13): 1159-1180.
[6] 朱慧丹, 周子晔, 王贤亲, 等. 探针药物法评价辣椒碱对大鼠CYP450的影响[J]. 中国卫生检验杂志, 2013, 23(18): 3474-3476.
[7] 郑天慧, 刘伟, 李淑萍, 等. 不同急性肝损伤大鼠模型对5种CYP450酶的影响[J]. 中国药学杂志, 2017, 52(12):1023-1028.
[8] 杜犀, 何新, 黄宇虹, 等. 应用Cocktail探针药物法分析中药对CYP450酶活性影响的研究进展[J]. 中国中药杂志, 2016, 41(24):4541-4549.
[9] 孙冰婷, 居文政, 谈恒山. Cocktail法研究CYP450酶活性影响因素的探讨[J]. 中国医院药学杂志, 2015, 35(6):558-562.
[10] Wen C, Cai J, Lin C, et al. Gradient elution liquid chromatography mass spectrometry determination of acetylcorynoline in rat plasma and its application to a pharmacokinetic study[J]. Xenobiotica, 2014, 44(8): 743-748.
[11] Ma J, Ding X, Sun C, et al. Development and validation a liquid chromatography mass spectrometry for determination of solasodine in rat plasma and its application to a pharmacokinetic study[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2014, 963: 24-28.
[12] Logan BK, Yeakel JK, Goldfogel G, et al. Dextromethorphan abuse leading to assault, suicide, or homicide[J]. J Forensic Sci, 2012, 57(5): 1388-1394.
[13] Miller SC. Dextromethorphan to dextrorphan: a pathway towards abuse liability[J]. Hum Psychopharmacol, 2011, 26(1): 89-90, author reply 91.
[14] Cai J, Dai DP, Geng PW, et al. Effects of 22 novel CYP2D6 variants found in the Chinese population on the bufuralol and dextromethorphan metabolisms in vitro[J]. Basic Clin Pharmacol Toxicol, 2016, 118(3): 190-199.
[15] Shin EJ, Lee PH, Kim HJ, et al. Neuropsychotoxicity of abused drugs: Potential of dextromethorphan and novel neuroprotective analogs of dextromethorphan with improved safety profiles in terms of abuse and neuroprotective effects[J]. J Pharmacol Sci, 2008, 106(1): 22-27.