摘要
目的建立快速、灵敏的液相色谱-串联质谱(LC-MS/MS)方法测定人血浆中布洛芬。方法血浆样品经液-液萃取后,以乙腈-甲醇-5 mmol·L-1醋酸铵-甲酸(450∶450∶100∶0.062 5)作为流动相,采用Zorbax Eclipse XDB-C18柱分离,通过电喷雾电离源以多反应监测(MRM)方式进行负离子检测。用于定量分析的离子反应分别为m/z205→m/z161(布洛芬)和m/z229→m/z185(内标,萘普生)。结果人血浆中布洛芬测定的线性范围为50.0～25 000μg·L-1,定量下限为50.0μg·L-1,日内、日间精密度(RSD)均小于8.5%,准确度(RE)在±2.5%以内,每个样品测试时间仅为4.0 min。结论pH值是影响布洛芬色谱行为和质谱响应的主要因素,优化后的方法具有快速、灵敏等特点,适用于布洛伪麻片中布洛芬的生物利用度和生物等效性研究。
Abstract
OBJECTIVE To developed a simple,sensitive and rapid liquid chromatography-tandem mass spectrometric method for the determination of ibuprofen in human plasma.METHODS Ibuprofen and the internal standard,naproxen,were processed from plasma by liquid-liquid extraction with n-hexane,and then chromatographed on a Zorbax Eclipse XDB-C18 column(4.6 mm×150 mm,5 μm),using acetonitrile-methanol-5 mmol·L-1 ammonium acetate-formic acid(450∶450∶100∶0.062 5) as the mobile phase.An API 4000 tandem mass spectrometer equipped with Turbo Ionspray ionization source was used as detector and was operated in the negative ion mode.Multiple reaction monitoring(MRM) with the precursor to product ion combinations of m/z 205→161 and m/z 229→185 were used to quantify ibuprofen and naproxen(IS),respectively.RESULTS The linear range of the calibration curve for ibuprofen was 50.0-25 000 μg·L-1.The limit of quantification was 50.0 μg·L-1 by using 25 μL plasma sample.Each sample was assayed within 4.0 min.CONCLUSION The method was proved to be rapid,sensitive and suitable for bioavailability and bioequivalence investigations of ibuprofen formulations.
关键词
布洛芬 /
液相色谱-串联质谱法 /
血浆浓度
{{custom_keyword}} /
Key words
ibuprofen /
liquid chromatography-tandem mass spectrometry /
plasma concentration
{{custom_keyword}} /
李黎;段小涛;刘茜;钟大放;陈笑艳.
液相色谱-串联质谱法快速测定人血浆中布洛芬[J]. 中国药学杂志, 2008, 43(21): 1657-1660
LI Li;DUN Xio-to;LIU Qin;ZHONG D-fng;CHEN Xio-yn.
Rapid Determination of Ibuprofen in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry Method [J]. Chinese Pharmaceutical Journal, 2008, 43(21): 1657-1660
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] DAVIES E F，AVERY G S. Ibuprofen， a review of its pharmac- olofical properties and therapeutic efficacy in rheumatic disorder[J] . Drugs， 1971， 2(5)：416-446.
[2] ZHANG W J，LOU J S，JIANG H，et al. Determination of ibuprofen and pseudoephedrine hydrochloride in plasma by HPLC[J] . Chin Pharm J (中国药学杂志)， 2006， 41(9)：701-703.
[3] ZHAO X L，CHEN D W，LI K X，et al. Sensitive liquid chromatographic assay for the simultaneous determination of ibuprofen and its prodrug，ibuprofen eugenol ester， in rat plasma[J] . Yakugaku Zasshi， 2005， 125 (9)：733-737.
[4] WANG P， QI M L， LIU L H， et al. Determination of ibuprofen in dog plasma by chromatography and application in pharmacokinetic studies of an ibuprofen prodrug in dogs[J] . J Pharm Biomed Anal， 2005，38(4)：714-719.
[5] ZHAO X， SUN P H， ZHOU Y， et al. Determination of ibuprofen in human serum by HPLC[J] . Chin J Clin Pharmacol， 2004， 20 (4)：295-298.
[6] FARRAR H， LETZIG L， GILL M. Validation of liquid chroma- tographic method for the determination of ibuprofen in human plasma[J] . J Chromatogr B， 2002，780(2)：341-348.
[7] WAY B A， WILHITE T R， SMITH C， et al. Measurement of plasma ibuprofen by gas chromatography-mass spectrometry[J] . J Clin Lab Anal， 1997，11(6)：336-339.
[8] GL OWKA F K， KARA ZNIEWICZ M. High performance cap- illary electrophoresis method for determination of ibuprofen enantiomers in human serum and urine[J] . Anal Chim Acta，2005，540(1)：95-102.
[9] BONATO P S， DEL LAMA M P， CARVALHO R. Enantiosel- ective determination of ibuprofen in plasma by high-performance liquid chromatography electrospray mass spectrometry[J] . J Chromatogr B， 2003，796(2)：413-420.
[10] SHAP V P， MIDHA K K， FINDLAY J W， et al. Bioanalytical method validation-A revisit with a decade of progress[J] . Pharm Res， 2000，17 (12)：1511-1517.
[11] ZHOU H， LIANG W， HU P， et al. Method of quantitative determination of ibuprofen and pseudoephedrine in plasma by liquid chromatography-tandem mass spectrometry[J] . J Chin Mass Spectrometry Society（质谱学报）， 2004，25(21)：157-158.
[12] SUN Y， TAKABA K， KIDO H， et al. Simultaneous determin- ation of arylpropionic acidic nonsteroidal anti-inflammatory drugs in pharmaceutical formulations and human plasma by HPLC with UV detection[J] . J Pharm Biomed Anal， 2003，30(5)：1611-1619.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
