Matrix Effects and Countermeasure of Liquid Chromatography-Tandem Mass Spectrometry in Bioanalysis

LIU Xiao-yun; CHEN Xiao-yan; ZHONG Da-fang

doi:10.7538/zpxb.2016.0214

Journal of Chinese Mass Spectrometry Society > 2017 > 38(4): 388-399. > DOI: 10.7538/zpxb.2016.0214 CSTR: 32365.14.zpxb.2016.0214

LIU Xiao-yun, CHEN Xiao-yan, ZHONG Da-fang. Matrix Effects and Countermeasure of Liquid Chromatography-Tandem Mass Spectrometry in Bioanalysis[J]. Journal of Chinese Mass Spectrometry Society, 2017, 38(4): 388-399. DOI: 10.7538/zpxb.2016.0214

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Matrix Effects and Countermeasure of Liquid Chromatography-Tandem Mass Spectrometry in Bioanalysis

Center for Drug Metabolism and Pharmacokinetics, Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China

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Abstract

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has the characteristics of high sensitivity, high selectivity and high throughput, and has become the mainstream approach for bioanalytical assays. It is widely used for the quantitative analysis of new drug entities (NCEs) and their metabolites in the discovery and development of new drugs. However, due to the complex composition of the biological sample matrix, the co-eluting material affects the ionization of the analyte, result in increases or decreases the mass spectral response of the analyte, thus affecting the accuracy and precision of the LC-MS/MS analysis method. In general, ion suppression is more common than ion enhancement. When the analytical method is established, if the ion suppression is not evaluated and corrected, the sensitivity of the analytical method will be seriously affected. Therefore, it is important to assess the matrix effect and use different strategies to eliminate or reduce the impact of matrix effects. In this paper, an overview was provided, including how matrix effect occurs, outline the methodologies used to assess the matrix effect in biological sample analysis and discuss the strategy of overcoming the matrix effect. Substances that cause matrix effects include endogenous substances and exogenous substances. Endogenous substances include phospholipid, salts, urea, metabolites and so on. Exogenous substances such as excipients, anticoagulants, stationary phase release materials and degradation products. At present, there are mainly two method to assess the matrix effect, one is post-extraction spike, the other is post-column infusion. The strategies to overcome the matrix effect including the use of stable-isotope labeled internal standard, derivatization of polar drugs, dilute the supernatant after precipitation of the protein, optimize sample pretreatment method, the chromatographic conditions and the mass spectrometry conditions. This paper provides examples of the application of our laboratory, focusing on the difficulties encountered and solutions in the establishment of LC-MS/MS analysis methods.
- liquid chromatography-tandem mass spectrometry (LC-MS/MS),
- pharmacokinetics,
- matrix effect

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[1]	JANUSCH F, KALTHOFF L, HAMSCHER G, et al. Evaluation and subsequent minimization of matrix effects caused by phospholipids in LC-MS analysis of biological samples[J]. Bioanalysis, 2013, 5(17): 2101-2114.
[2]	王立琦，贺利民，曾振灵，等. 液相色谱-串联质谱检测兽药残留中的基质效应研究进展[J]. 质谱学报，2011,32(6):321-332.WANG Liqi, HE Limin, ZENG Zhenling, et al. Progress in matrix effect of veterinary drug residues analysis by high-performance liquid chromatography tandem mass spectrometry[J]. Journal of Chinese Mass Spectrometry Society, 2011, 32(6): 321-332(in Chinese).
[3]	冯晓杰，杜丽英，冯章英，等. LC-MS/MS法测定人血药浓度的基质效应研究进展[J]. 中国新药杂志，2015,24(13):1488-1497.FENG Xiaojie, DU Liying, FENG Zhangying, et al. Research progress of matrix effect in determining blood concentration by LC-MS/MS[J]. Chinese Journal of New Drugs, 2015, 24(13): 1488-1497(in Chinese).
[4]	苏萌，艾连峰. 液相色谱-串联质谱基质效应及其消除方法[J].食品安全质量检测方法，2014,5(2):511-515.SU Meng, AI Lianfeng. Matrix effects and elimination methods of liquid chromatography-tandem mass spectrometry[J]. Journal of Food Safety and Quality, 2014, 5(2): 511-515(in Chinese).
[5]	SALATTI-DORADO J A, CABALLERO-CASERO N, SICILIA M D, et al. The use of a restricted access volatile supramolecular solvent for the LC/MS-MS assay of bisphenol A in urine with a significant reduction of phospholipids-based matrix effects[J]. Analytica Chimica Acta, 2017, (950): 71-79.
[6]	TRUFELLI H, PALMA P, FAMIGLINI G, et al. An overview of matrix effects in liquid chromatography-mass spectrometry[J]. Mass Spectrometry Reviews, 2011, 30(3): 491-509.
[7]	FUREY A, MORIARTY M, BANE V, et al. Ion suppression: a critical review on causes, evaluation, prevention and applications[J]. Talanta, 2013, 115(115): 104-122.
[8]	ARRIVAULT S, GUENTHER M, FRY S C, et al. Synthesis and use of stable-isotope-labeled internal standards for quantification of phosphorylated metabolites by LC-MS/MS[J]. Analytical Chemistry, 2015, 87(13): 6896-6904.
[9]	YANG Y, XU Q F, ZHOU L, et al. High-throughput salting-out-assisted liquid-liquid extraction for the simultaneous determination of atorvastatin, ortho-hydroxyatorvastatin, and para-hydroxyatorvastatin in human plasma using ultrafast liquid chromatography with tandem mass spectrometry[J]. Journal of Separation Science, 2015, 38(6): 1026-1034.
[10]	DENG P, JI C, DAI X J, et al. Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry[J]. Journal of Chromatography B, 2015, (989): 71-79.
[11]	DIAO X X, MA Z Y, LEI P, et al. Enantioselective determination of 3-n-butylphthalide (NBP) in human plasma by liquid chromatography on a teicoplanin-based chiral column coupled with tandem mass spectrometry[J]. Journal of Chromatography B, 2013, (939): 67-72.
[12]	DIAO X X, MA Z Y, WANG H, et al. Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards[J]. Journal of Pharmaceutical and Biomedical Analysis, 2013, (78/79): 19-26.
[13]	CHEN M X, LIU K, ZHONG D F, et al. Trimethylsilyldiazomethane derivatization coupled with solid-phase extraction for the determination of alendronate in human plasma by LC-MS/MS[J]. Analytical and Bioanalytical Chemistry, 2012, 402(2): 791-798.
[14]	YANG Y, LIU C, ZHANG Y F, et al. On-cartridge derivatization coupled with solid-phase extraction for the ultra-sensitive determination of minodronic acid in human plasma by LC-MS/MS method[J]. Journal of Pharmaceutical and Biomedical Analysis, 2015, (114): 408-415.
[15]	ZHONG K, GAO Z W, LI Q, et al. A chiral high-performance liquid chromatography-tandem mass spectrometry method for the stereospecific determination of morinidazole in human plasma[J]. Journal of Chromatography B, 2014, (961): 49-55.
[16]	DU J B, MA Z Y, ZHANG Y F, et al. Enantioselective determination of ornidazole in human plasma by liquid chromatography-tandem mass spectrometry on a Chiral-AGP column[J]. Journal of Pharmaceutical and Biomedical Analysis, 2013, 86(1): 182-188.
[17]	DU J B, MA Z Y, ZHANG Y F, et al. Simultaneous determination of ornidazole and its main metabolites in human plasma by LC-MS/MS: application to a pharmacokinetic study[J]. Bioanalysis, 2014, 6(18): 2343-2356.
[18]	LIU J, WANG L, HU W J, et al. Development of a UHPLC-MS/MS method for the determination of plasma histamine in various mammalian species[J]. Journal of Chromatography B, 2014, (971): 35-42.
[19]	LU Y M, SUN Z M, ZHANG Y F, et al. Simultaneous quantification of 22R and 22S epimers of budesonide in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry:application in a stereoselective pharmacokinetic study[J]. Journal of Chromatography B, 2013, (921/922): 27-34.
[20]	YANG Y, YU J H, LU Y M, et al. High-sensitivity liquid chromatography-tandem mass spectrometry method for the simultaneous determination of sodium picosulfate and its three major metabolites in human plasma[J]. Journal of Chromatography B, 2013, (915/916): 1-7.
[21]	WANG H D, DENG P, CHEN X Y, et al. Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of febuxostat in human plasma[J]. Biomedical Chromatography, 2013, 27(1): 34-38.
[22]	LIU K, ZHONG D F, ZOU H Y, et al. Determination of tegafur, 5-fluorouracil, gimeracil and oxonic acid in human plasma using liquid chromatography-tandem mass spectrometry[J]. Journal of Pharmaceutical and Biomedical Analysis, 2010, 52(4): 550-556.
[23]	ZHAN Y, CHEN X Y, ZHONG D F. Quantifying tetrapeptide SS-20 in rat plasma using hydrophilic interaction liquid chromatography coupled with electrospray ionization tandem mass spectrometry[J]. Journal of Chromatography B, 2011, 879(30): 3353-3359.
[24]	DENG P, CHEN X Y, ZHONG D F. Quantification of polar drugs in human plasma with liquid chromatography-tandem mass spectrometry[J]. Bioanalysis, 2009, 1(1): 187-203.
[25]	ZHANG Y, CHEN X Y, LI X Y, et al. Development of a liquid chromatographic-tandem mass spectrometric method with precolumn derivatization for the determination of dencichine in rat plasma[J]. Analytica Chimica Acta, 2006, 566(2): 200-206.
[26]	PARK J S, PARK M Y, CHO Y J, et al. Anti-inflammatory effect of erdosteine in lipopolysaccharide-stimulated RAW 264.7 cells[J]. Inflammation, 2016, 39(4): 1573-1581.
[27]	金经，陈笑艳，张逸凡，等. 柱前衍生化 LC-MS/MS 法同时测定人血浆中厄多司坦及其活性代谢物[J]. 药学学报，2013,48(3):395-400.JIN Jing, CHEN Xiaoyan, ZHANG Yifan, et al. Simultaneous determination of erdosteine and its active metabolite in human plasma by liquid chromatography-tandem mass spectrometry with pre-column derivatization[J]. Acta Pharmaceutica Sinica, 2013, 48(3): 395-400(in Chinese).
[28]	CHIU M L, LAWI W, SNYDER S T, et al. Matrix effects—a challenge toward automation of molecular analysis[J]. Journal of the Association for Laboratory Automation, 2010, 15(3): 233-242.
[29]	DING J F, CHEN X Y, DAI X J, et al. Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study[J]. Journal of Chromatography B, 2012, (895): 108-115.
[30]	YANG Y, LIU K, ZHONG D F, et al. Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry[J]. Journal of Chromatography B, 2012, (895/896): 25-30.
[31]	WANG Y, CHEN X Y, SUN Z M, et al. Development and validation of a sensitive LC-MS/MS assay for simultaneous quantitation of ranolazine and its three metabolites in human plasma[J]. Journal of Chromatography B, 2012, (889/890): 10-16.
[32]	张娟，陈笑艳，戴晓健，等. 正负离子切换液相色谱-串联质谱法同时测定人血浆中头孢他啶和他唑巴坦[J]. 药物分析杂志，2012,32(1):20-25.ZHANG Juan, CHEN Xiaoyan, DAI Xiaojian, et al. Simultaneous determination of ceftazidime and tazobactam in human plasma with sequential positive and negative ionization liquid chromatography-tandem mass spectrometry detection[J]. Chinese Journal Pharmaceutical Analysis, 2012, 32(1): 20-25(in Chinese).
[33]	石荣伟，刘可，陈笑艳，等. 亲水作用色谱串联质谱法测定人血浆中的拉米夫定[J]. 药物分析杂志，2011,31(8):1448-1452.SHI Rongwei, LIU Ke, CHEN Xiaoyan, et al. Determination of lamivudine in human plasma by hydrophilic interaction chromatography (HILIC) tandem mass spectrometry[J]. Chinese Journal Pharmaceutical Analysis, 2011, 31(8): 1448-1452(in Chinese).
[34]	NEVILLE D, HOUGHTON R, GARRETT S. Efficacy of plasma phospholipid removal during sample preparation and subsequent retention under typical UHPLC conditions[J]. Bioanalysis, 2012, 4(7): 795-807.
[35]	ISOKAWA M, KANAMORI T, FUNATSU T, et al. Recent advances in hydrophilic interaction chromatography for quantitative analysis of endogenous and pharmaceutical compounds in plasma samples[J]. Bioanalysis, 2014, 6(18):2421-2439.
[36]	SILVESTRO L, TARCOMNICU I, SAVU S R. Matrix effects in mass spectrometry combined with separation methods-comparison HPLC, GC and discussion on methods to control these effects[J]. Tandem Mass Spectrometry-Molecular Characterization, 2013: 3-37.
[37]	CRUZ-CORREA O F, LEÓN-CACHÓN R B R, BARRERA-SALDAÑA H A, et al. Prediction of atorvastatin plasmatic concentrations in healthy volunteers using integrated pharmacogenetics sequencing[J]. Pharmacogenomics, 2017, 18(2): 121-131.
[38]	SINGH P, MITTAL R, SHARMA G C, et al. Ornidazole: comprehensive profile[J]. Profiles of Drug Substances, Excipients and Related Methodology, 2003, 30(3): 123-184.
[39]	DU J B, YOU T G, CHEN X Y, et al. Stereoselective glucuronidation of ornidazole in humans: predominant contribution of UDP-glucuronosyltransferases 1A9 and 2B7[J]. Drug Metabolism and Disposition, 2013, 41(7): 1306-1318.

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