UPLC-MS/MS法同时测定人血浆中普拉克索和金刚烷胺浓度
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摘要
目的:建立利用UPLC-MS/MS法同时测定人血浆中普拉克索和金刚烷胺的分析方法。方法:在碱性条件下,血浆样品经乙酸乙酯萃取。采用Acquity UPLC BEH C_(18)(2.1 mm×50 mm,1.7 m)色谱柱,甲醇(A)-0.01%甲酸水(B)为流动相,梯度洗脱,流速0.2 mL·min~(-1),柱温为30℃;采用电喷雾离子源、正离子方式、多反应监测(RRM),普拉克索离子反应为m/z 212→153,金刚烷胺为m/z 152→135,内标伪麻黄碱为m/z 166→148。结果:普拉克索血浆质量浓度在10～1 200 pg·m L~(-1),金刚烷胺在0.7～700 ng·m L~(-1)内线性关系良好,两者日内、日间RSD均小于9.8%,方法回收率均在100.3%～106.0%之间。所测30例帕金森患者中,普拉克索平均谷浓度为(643.61±243.19)pg·mL~(-1),金刚烷胺平均谷浓度为(551.67±81.14)ng·mL~(-1)。结论:建立的检测方法可用于同时测定人体血浆中普拉克索和金刚烷胺的浓度。
Objective:To develop a sensitive ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for the simultaneous determination of pramipexole and amantadine in human plasma.Methods:The plasma sample was first extracted with acetic ether in alkaline conditions.UPLC-MS/MS was performed on an Acquity UPLC BEH C_(18)(2.1 mm×50 mm,1.7 m) column with the mobile phase consisting of methanol(A) and 0.01% aqueous formic acid(B) in gradient elution.The flow rate was controlled at 0.2 mL·min~(-1),and the column temperature was set at 30 ℃.A mass spectrometer equipped with electrospray ionization source was used as detector operate in the positive ion mode.Multiple reaction monitoring(RRM) mode was performed using the transition of m/z 212 → 153,m/z 152 → 135 and m/z 166 → 148 to quantify pramipexole,amantadine and internal standard of pseudoephedrine,respectively.Results:In human plasma,the standard curves of pramipexole and amantadine were linear from 10-1 200 pg·mL~(-1) and 0.7～700 ng·mL~(-1),the overall relative recoveries ranged from 100.3%-106.0% with the intra-and inter-day RSDs both below 9.8%.In 30 cases of Parkinson's patients,the average trough concentration of pramepexole and amantadine was(643.61± 243.19) pg·mL~(-1) and(551.67±81.14) ng·mL~(-1),respectively.Conclusion:The established method can be used to simultaneously determine pramipexole and amantadine.
Objective:To develop a sensitive ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for the simultaneous determination of pramipexole and amantadine in human plasma.Methods:The plasma sample was first extracted with acetic ether in alkaline conditions.UPLC-MS/MS was performed on an Acquity UPLC BEH C_(18)(2.1 mm×50 mm,1.7 m) column with the mobile phase consisting of methanol(A) and 0.01% aqueous formic acid(B) in gradient elution.The flow rate was controlled at 0.2 mL·min~(-1),and the column temperature was set at 30 ℃.A mass spectrometer equipped with electrospray ionization source was used as detector operate in the positive ion mode.Multiple reaction monitoring(RRM) mode was performed using the transition of m/z 212 → 153,m/z 152 → 135 and m/z 166 → 148 to quantify pramipexole,amantadine and internal standard of pseudoephedrine,respectively.Results:In human plasma,the standard curves of pramipexole and amantadine were linear from 10-1 200 pg·mL~(-1) and 0.7～700 ng·mL~(-1),the overall relative recoveries ranged from 100.3%-106.0% with the intra-and inter-day RSDs both below 9.8%.In 30 cases of Parkinson's patients,the average trough concentration of pramepexole and amantadine was(643.61± 243.19) pg·mL~(-1) and(551.67±81.14) ng·mL~(-1),respectively.Conclusion:The established method can be used to simultaneously determine pramipexole and amantadine.
引文
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[8]CELMA C,ALLUE JA,PRUNONOSA J,et al.Simultaneous determination of paracetamol and chlorpheniramine in human plasmaby liquid chromatography-tandem mass spectromatography[J].J Chromatogr A,2000,870(1-2):77
[9]RAKESTRAW D.Determination of amantadine in human plasma by capillary gas chromatography using electron-capture detection following derivatization with pentafluorobenzoyl chloride[J].J Pharm Biomed Anal,1993,11(8):699
[10]李华,陈笑艳,施孝金.高灵敏度液相色谱-串联质谱法测定人血浆中普拉克索[J].药物分析杂志,2011,31(2):330LI H,CHEN XJ.LC-MS/MS determination of pramipexole in human plasma[J].Chin J Pharm Anal,2011,31(2):330
[11]BHARATHI DV,HOTHA KK,SAGAR PV,et al.Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma:application to a clinical pharmacokinetic study[J].Biomed Chromatogr,2009,23(2):212
[12]DIAO L,SHU Y,POLLI JE,et al.Uptake of pramipexole by human organic cation transporters[J].Mol Pharm,2010,7(4):1342
[2]MARTINEZ-CORRAL M,KUL ISEVSKY J.Pramipexole and parkinsonps disease,an update[J].Rev Neurol,2008,46(1):49
[3]HAMETNER EM,SEPPI K,POEWE W.Role and clinical utility of pramipexole extended release in the treatment of early Parkinson’s disease[J].Clin Interv Aqing,2012,7(83):8
[4]邓顺周,李润铭.帕金森病治疗药物[J].食品与药品,2007,9(5):28DENG SZ,LI RM.Antiparkison drugs[J].Food Drug,2007,9(5):28
[5]GORALSKI KB.The cation transporters r OCT 1 and r OCT 2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules[J].J Pharmacol Exp Ther,2002,303(3):959
[6]MOTOHASHI H,SAKURAI Y,SAITO H,et al.Gene expression levels and immunoloc alization of organic cation transporters in the human kidney[J].J Am Soc Nephrol,2002,13(4):886
[7]WU MJ,ING TS,SOUNG LS,et al.Amantadine hydrochloride pharmacokinetics in patients with impaired renal function[J].Clin Nephrol,1982,17(1):19
[8]CELMA C,ALLUE JA,PRUNONOSA J,et al.Simultaneous determination of paracetamol and chlorpheniramine in human plasmaby liquid chromatography-tandem mass spectromatography[J].J Chromatogr A,2000,870(1-2):77
[9]RAKESTRAW D.Determination of amantadine in human plasma by capillary gas chromatography using electron-capture detection following derivatization with pentafluorobenzoyl chloride[J].J Pharm Biomed Anal,1993,11(8):699
[10]李华,陈笑艳,施孝金.高灵敏度液相色谱-串联质谱法测定人血浆中普拉克索[J].药物分析杂志,2011,31(2):330LI H,CHEN XJ.LC-MS/MS determination of pramipexole in human plasma[J].Chin J Pharm Anal,2011,31(2):330
[11]BHARATHI DV,HOTHA KK,SAGAR PV,et al.Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma:application to a clinical pharmacokinetic study[J].Biomed Chromatogr,2009,23(2):212
[12]DIAO L,SHU Y,POLLI JE,et al.Uptake of pramipexole by human organic cation transporters[J].Mol Pharm,2010,7(4):1342