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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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HPLC-MS/MS法测定人血浆中孟鲁司特浓度及其在药动学中的应用

A validated HPLC-MS/MS method for determination of montelukast in human plasma and its application in pharmacokinetic study

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (3):399-405
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立HPLC-MS/MS法测定人血浆中的孟鲁司特浓度,并对健康人群空腹及餐后口服孟鲁司特钠颗粒后的药代动力学进行研究。方法:以孟鲁司特-d6为内标,经乙腈沉淀蛋白后,采用高效液相色谱分离系统,Phenomenex luna C18(50 mm×2.1 mm,5 μm)色谱柱,流动相为乙腈-水-甲酸(80:20:0.01)。采用质谱检测系统,电喷雾离子源(ESI源),正离子扫描,多反应监测模式(MRM)监测m/z 586.6→422.3(孟鲁司特)及m/z 592.0→427.2(孟鲁司特-d6)。12名健康受试者单剂量空腹或餐后口服孟鲁司特钠颗粒0.5 g后采集血浆样品,以HPLC-MS/MS法测定血浆中孟鲁司特的浓度,计算药动学参数并进行统计分析。结果:孟鲁司特质量浓度在2.060~309.0 ng·mL-1范围内与色谱响应呈现良好的线性关系,定量下限为2.060 ng·mL-1。健康中国受试者单剂量空腹及餐后口服孟鲁司特钠颗粒0.5 g后主要药动学参数分别为Cmax (173.8±43.0) ng·mL-1、(150.5±19.8) ng·mL-1Tmax (2.56±0.62) h、(5.38±1.49) h,AUC0-t (1 305±345) ng·h·mL-1、(1 674±329) ng·h·mL-1,AUC0~∞(1 357±368) ng·h·mL-1、(1 761±356) ng·h·mL-1。统计结果表明,除Tmax外,其余参数在空腹及餐后之间的差异均不具有统计学意义。结论:本方法经完全方法学验证,适用于人体血浆中孟鲁司特的测定,并可用于临床药动学研究。药动学研究表明高脂餐不影响孟鲁司特钠颗粒在体内的吸收程度,但是明显延迟其吸收速度。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To establish a rapid and simple method for the determination of montelukast in human plasma,and study the pharmacokinetics of montelukast sodium granules in Chinese healthy volunteers.Methods: Montelukast-d6 acted as the internal standard,and the separation of plasma was performed on a Phenomenex luna C18(50 mm×2.1 mm,5 μm) column after precipitated by acetonitrile with a mobile phase comprising of acetonitrile-water-formic acid(80:20:0.01) at a flow rate of 0.5 mL·min-1,and then detected on the MS system.Ions monitored in the multiple reaction monitoring(MRM) mode were m/z 586.6→422.3 for montelukast and m/z 592.0→427.2 for montelukast-d6,respectively.The pharmacokinetic characteristics of montelukast sodium granules were investigated in 12 Chinese healthy volunteers after single oral administration of 0.5 g montelukast sodium granules under the condition of fasting or fed,plasma samples collected were detected by the validated HPLC-MS/MS method.Results: Peak area ratio of the drug to the internal standard was used for the quantification of montelukast in plasma samples,the linearity were found to be in the range of 2.060-309.0 ng·mL-1 and the limit of quantification was 2.060 ng·mL-1.The analyte was proved to be stable under all the required conditions.The total runtime of analyte was only 2 minutes.The pharmacokinetic features of montelukast in healthy Chinese people after an oral administration were as follows:Cmax(173.8±43.0)ng·mL-1(fasting),(150.5±19.8) ng·mL-1(fed);Tmax(2.56±0.62)h(fasting),(5.38±1.49)h(fed);AUC0-t(1 305±345) ng·h·mL-1(fasting),(1 674±329)ng·h·mL-1(fed);AUC0~∞(1 357±368)ng·h·mL-1(fasting) and(1 761±356) ng·h·mL-1(fed).The differences in all parameters between fasting and fed were not statistically significant except Tmax.Conclusion: This is a rapid and simple method to determine montelukast in human plasma and is applicable to the pharmacokinetic study.The results of pharmacokinetic study indicated that high fat meal did not affect the AUC of montelukast sodium in Chinese healthy volunteers,but it did slow down the absorption rate of montelukast in Chinese people.

-----参考文献:---------------------------------------------------------------------------------------
[1] JONES TR,LABELLE M,BELLEY M,et al.Pharmacology of montelukast sodium (Singulair),a potent and selective leukotriene D4 receptor antagonist[J].Canadian J Physiol Pharmacol,1995,73(2):191
[2] VIRCHOW JC,FAEHNDRICH S,NASSENSTEIN C,et al.Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells[J].Clin Exp Allergy,2001,31(6):836
[3] ABUALHASAN ANZ,WATSON DG,MOUSA A,et al.Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method[J].Drug Des Devel Ther,2015,9:5315
[4] MUPPAVARAPU R,GUTTIKAR S,RAJAPPAN M,et al.Sensitive LC-MS/MS-ESI method for simultaneous determination of montelukast and fexofenadine in human plasma:application to a bioequivalence study[J].Biomed Chromatogr,2014,28(8):1048
[5] 同丽萍,关月,刘渝,等.对孟鲁司特钠分散片的人体生物等效性研究[J].药学服务与研究,2010,10(5):371 TONG LP,GUAN Y,LIU Y,et al.Bioequivalence of montelukast sodium dispersible in human body[J].Pharm Care Res,2010,10(5):371
[6] CHALLA BR,AWEN BZ,CHANDU BR,et al.Method development and validation of montelukast in human plasma by HPLC coupled with ESI-MS/MS:application to a bioequivalence study[J].Sci Pharm,2010,78(3):411
[7] PATEL NK,SUBBAIAH G,SHAH H,et al.Rapid determination of montelukast in human plasma by LC-ESI-MS/MS and its application to a bioequivalence study[J].Anal Lett,2009,42(13):2041
[8] BHARHTHI DV,HOTHA KK,JAGADEESH B,et al.Quantification of montelukast,a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography-mass spectrometry:validation and its application to a human pharmacokinetic study[J].biomed chromatogr,2009,23(8):804
[9] SRIPALAKIT P,KONGTHONG B,SARAPHANCHOTIWITTHAYA A.A simple bioanalytical assay for determination of montelukast in human plasma:application to a pharmacokinetic study[J].J Chromatogr B Anal Technol Biomed Life Sci,2008,869(1-2):38
[10] 张相林,李凯鹏,丁庆明,等.孟鲁司特钠药动学及其国产片剂/咀嚼片剂人体相对生物利用度研究[J].Chin J New Drugs,2006,15(9):728 ZHANG XL,LI KP,DING QM,et al.Pharmacokinetics and relative bioavilability of montelukast film-coated tablets and chewable tablets[J].Chin J New Drugs,2006,15(9):728
[11] ALASARRA IA,Development of a stability-indicating HPLC method for the determination of montelukast in tablets and human plasma and its application to pharmacokinetic and stability studies[J].Saudi Pharm J,2004,12(4):136
[12] FEY C,THYROFF-FRIESINGER U,JONES S.Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults[J].Clin Transl Allergy,2014,(4):29
[13] 于广华,张凤武.高效液相色谱法测定孟鲁司特钠散的含量[J].黑龙江医药,2016,26(1):18 YU GH,ZHANG FW.Determination of the content of montelukast sodium by high performance liquid chromatography(HPLC)method[J].Heilongjiang Med J,2016,26(1):18
[14] VEKARIA H,LIMBASIYA V,PATEL P.Development and validation of RP-HPLC method for simultaneous estimation of montelukast sodium and fexofenadine hydrochloride in combined dosage form[J].J Pharm Res,2013,6(1):134
[15] SINGH RR,RATHNAM MV.A stability-indicating method for the estimation of montelukast sodium and fexofenadine hydrochloride in pharmaceutical preparations[J].Intern J Pharm Pharm Sci,2011,4(2):587
[16] RASHMITHA N,RAJ TJ,SRINIVAS N,et al.A validated RP-HPLC method for the determination of impurities in montelukast sodium[J].E-J Chem,2009,7(2):555
[17] RADHAKRISHNANAND P,SUBBA RAO DV,SURENDRANATH KV,et al.A validated LC method for determination of the enantiomeric purity of montelukast sodium in bulk drug samples and pharmaceutical dosage forms[J].Chromatographia,2008,68(3-4):263
[18] TANDULWARDKA SS,MORE SJ,RATHORE AS,et al.Method development and validation for the simultaneous determination of fexofenadine hydrochloride and montelukast sodium in drug formulation using normal phase high-performance thin-layer chromatography[J].ISRN Anal Chem,2012,2012:1
[19] LIDA L,HAIYUNG C,JAMIE JZ,et al.Determination of montelukast (MK-0476) and its S-enantiomer in human plasma by stereoselective high-performance liquid chromatography with column-switching[J].J Pharm Biomed Anal,1997,15:631
[20] AL-OMARI MM,ZOUBI RM,HASAN EI,et al.Effect of light and heat on the stability of montelukast in solution and in its solid state[J].J Pharm Biomed Anal,2007,45(3):465

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