LC-MS/MS法同时测定人血浆中万古霉素和去甲万古霉素的质量浓度
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摘要
目的建立一种简单、快速的同时测定人血浆中万古霉素和去甲万古霉素质量浓度的LC-MS/MS方法。方法以利奈唑胺为内标,血浆经高氯酸沉淀蛋白,加入2倍量水,离心,上清液用二氯甲烷萃取后进样分析;色谱柱为Hypersil GOLD aQ,1mL·L-1甲酸水溶液-甲醇梯度洗脱,流速为0.3mL·min-1;离子源为可加热电喷雾离子源,正离子检测,扫描方式为选择反应监测(SRM),万古霉素、去甲万古霉素和利奈唑胺的检测离子对分别为m/z725.7→144.2,m/z718.3→144.2和m/z338.3→296.0。结果各样品分析时间均为8min,血浆中万古霉素和去甲万古霉素的质量浓度在0.01～10μg·mL-1范围内线性关系良好,最低定量限均为10ng·mL-1,两药测定的日内和日间精密度RSD值小于15%,日内和日间相对误差在±15%以内。万古霉素和去甲万古霉素的提取回收率分别为74.16%～76.79%和73.01%～81.11%,基质效应分别为98.86%～108.69%和95.97%～109.64%。万古霉素和去甲万古霉素血浆样品在冻融、室温下保存24h和-80℃保存1个月的条件下稳定。结论建立的LC-MS/MS分析方法简便、快速、灵敏、准确,可同时测定人血浆中万古霉素和去甲万古霉素的质量浓度,并用于临床血药质量浓度的监测。
Objective To establish a simple and rapid LC-MS/MS method for simultaneous determination of the concentrations of vancomycin and norvancomycin in human plasma.Methods Linezolid was used as an internal standard,and plasma sample was deproteinized by adding perchloric acid.After protein precipitation,water was added to increase recovery,and the sample was centrifuged and the resulting supernatant was extracted with dichloromethane before analysis.Separation was achieved on a Hypersil GOLD aQ column with a mobile phase composed of 1mL·L-1 formic acid and methanol in gradient elution mode at a flow rate of0.3mL·min-1.The ionization source was heated electrospray source ionization(HESI),and selective reaction monitoring(SRM)in positive ion mode was used to determine the analytes.The precursor-product ion pairs used for SRM were m/z725.7→144.2,m/z718.3→144.2and m/z338.3→296.0for vancomycin,norvancomycin and internal standard,respectively.Results Total run time for each sample was 8min.The proposed method was linear over the range 0.01-10μg·mL-1 for both vancomycin and norvancomycin,and the lower limit of quantification(LLOQ)was 10ng·mL-1 for both of them.Intraday and interday precision were within 15%,and intraday and interday relative errors were within±15%.Recoveries were ranged from 74.16%to 76.79%and from 73.01%to 81.11%for vancomycin and norvancomycin respectively,and matrix effects of vancomycin and norvancomycin were within 98.86%-108.69%and 95.97%-109.64%,respectively.Vancomycin and norvancomycin were stable after freeze-thaw cycles and during storage at room temperature for 24 hand at-80℃for up to 1month.Conclusion A simple,rapid,sensitive and accurate LC-MS/MS method for simultaneous determination of vancomycin and norvancomycin in human plasma was developed,and was successfully applied to therapeutic drug monitoring.
Objective To establish a simple and rapid LC-MS/MS method for simultaneous determination of the concentrations of vancomycin and norvancomycin in human plasma.Methods Linezolid was used as an internal standard,and plasma sample was deproteinized by adding perchloric acid.After protein precipitation,water was added to increase recovery,and the sample was centrifuged and the resulting supernatant was extracted with dichloromethane before analysis.Separation was achieved on a Hypersil GOLD aQ column with a mobile phase composed of 1mL·L-1 formic acid and methanol in gradient elution mode at a flow rate of0.3mL·min-1.The ionization source was heated electrospray source ionization(HESI),and selective reaction monitoring(SRM)in positive ion mode was used to determine the analytes.The precursor-product ion pairs used for SRM were m/z725.7→144.2,m/z718.3→144.2and m/z338.3→296.0for vancomycin,norvancomycin and internal standard,respectively.Results Total run time for each sample was 8min.The proposed method was linear over the range 0.01-10μg·mL-1 for both vancomycin and norvancomycin,and the lower limit of quantification(LLOQ)was 10ng·mL-1 for both of them.Intraday and interday precision were within 15%,and intraday and interday relative errors were within±15%.Recoveries were ranged from 74.16%to 76.79%and from 73.01%to 81.11%for vancomycin and norvancomycin respectively,and matrix effects of vancomycin and norvancomycin were within 98.86%-108.69%and 95.97%-109.64%,respectively.Vancomycin and norvancomycin were stable after freeze-thaw cycles and during storage at room temperature for 24 hand at-80℃for up to 1month.Conclusion A simple,rapid,sensitive and accurate LC-MS/MS method for simultaneous determination of vancomycin and norvancomycin in human plasma was developed,and was successfully applied to therapeutic drug monitoring.
引文
[1] Rybak M,Lomaestro B,Rotschafer J C,et al.Therapeutic monitoring of vancomycin in adult patients:a consensus review of the American society of health-system pharmacists,the infectious diseases society of America,and the society of infectious diseases pharmacists[J].Am J Health-Syst Pharm,2009,66(1):82-98.
[2] Liu C,Bayer A,Cosgrove S E,et al.Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children:executive summary[J].Clin Infect Dis,2011,52(3):285-292.
[3]陈佰义,管向东,何礼贤,等.万古霉素临床应用中国专家共识(2011版)[J].中国新药与临床杂志,2011,30(8):561-573.
[4] Zhang J,Zhang Y,Shi Y,et al.Population pharmacokinetic and pharmacodynamic modeling of norvancomycin[J].Eur J Clin Microbiol Infect Dis,2008,27(4):275-284.
[5]彭斯维,陈永刚,邹吉利.酶放大免疫法测定去甲万古霉素的血药浓度[J].广东药学院学报,2014,30(5):553-558.
[6]黄晓会,刘艳,张健.HPLC法测定人血清中万古霉素及去甲万古霉素浓度及临床应用[J].中国药物应用与监测,2014,11(2):92-94.
[7]唐云彪,张萌萌,隋因,等.LC-MS/MS法测定人血浆中万古霉素的血药浓度[J].药物分析杂志,2013,33(9):1501-1506.
[8] Cass R T,Villa J S,Karr D E,et al.Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns[J].Rapid Commun Mass Spectrom,2001,15:406-412.
[9] Shibata N,Ishida M,Prasad Y V R,et al.Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography-tandem mass spectrometry and oral bioavailability in rats[J].J Chromatogr B Analyt Technol Biomed Life Sci,2003,789(2):211-218.
[10]Bijleveld Y,de Haan T,Toersche J,et al.A simple quantitative method analysing amikacin,gentamicin,and vancomycin levels in human newborn plasma using ion-pair liquid chromatography/tandem mass spectrometry and its applicability to a clinical study[J].J Chromatogr B Analyt Technol Biomed Life Sci,2014,951-952:110-118.
[11]Oyaert M,Peersman N,Kieffer D,et al.Novel LC-MS/MS method for plasma vancomycin:comparison with immunoassays and clinical impact[J].Clin Chim Acta,2015,441:63-70.
[12]Ahsman M J,Wildschut E D,Tibboel D,et al.Microanalysis ofβ-lactam antibiotics and vancomycin in plasma for pharmacokinetic studies in neonates[J].Antimicrob Agents Chemother,2009,53(1):75-80.
[13]Zhang T,Watson D G,Azike C,et al.Determination of vancomycin in serum by liquid chromatography-high resolution full scan mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,857(2):352-356.
[14]程晓亮,尤海生,王茂义,等.LC-MS/MS法同时测定人血浆中紫杉醇和多西他赛的质量浓度[J].西北药学杂志,2017,32(5):580-584.
[15]Wu X J,Zhang J,Yu J C,et al.Establishment of norvancomycin fluorescence polarization immunoassay for therapeutic drug monitoring[J].J Antibiot,2012,65(1),35-39.
[16]Matuszewski B K,Constanzer M L,Chavez-Eng C M.Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS[J].Anal Chem,2003,75(1):3019-3030.
[17]Jiang H L,Cao H C,Zhang Y,et al.Systematic evaluation of supported liquid extraction in reducing matrix effect and improving extraction efficiency in LC-MS/MS based bioanalysis for 10 model pharmaceutical compounds[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,891-892:71-80.
[18]Ismaiel O A,Zhang T Y,Jenkins R G,et al.Investigation of endogenous blood plasma phospholipids,cholesterol and glycerides that contribute to matrix effects in bioanalysis by liquid chromatography/mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2010,878(31):3303-3316.
[2] Liu C,Bayer A,Cosgrove S E,et al.Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children:executive summary[J].Clin Infect Dis,2011,52(3):285-292.
[3]陈佰义,管向东,何礼贤,等.万古霉素临床应用中国专家共识(2011版)[J].中国新药与临床杂志,2011,30(8):561-573.
[4] Zhang J,Zhang Y,Shi Y,et al.Population pharmacokinetic and pharmacodynamic modeling of norvancomycin[J].Eur J Clin Microbiol Infect Dis,2008,27(4):275-284.
[5]彭斯维,陈永刚,邹吉利.酶放大免疫法测定去甲万古霉素的血药浓度[J].广东药学院学报,2014,30(5):553-558.
[6]黄晓会,刘艳,张健.HPLC法测定人血清中万古霉素及去甲万古霉素浓度及临床应用[J].中国药物应用与监测,2014,11(2):92-94.
[7]唐云彪,张萌萌,隋因,等.LC-MS/MS法测定人血浆中万古霉素的血药浓度[J].药物分析杂志,2013,33(9):1501-1506.
[8] Cass R T,Villa J S,Karr D E,et al.Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns[J].Rapid Commun Mass Spectrom,2001,15:406-412.
[9] Shibata N,Ishida M,Prasad Y V R,et al.Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography-tandem mass spectrometry and oral bioavailability in rats[J].J Chromatogr B Analyt Technol Biomed Life Sci,2003,789(2):211-218.
[10]Bijleveld Y,de Haan T,Toersche J,et al.A simple quantitative method analysing amikacin,gentamicin,and vancomycin levels in human newborn plasma using ion-pair liquid chromatography/tandem mass spectrometry and its applicability to a clinical study[J].J Chromatogr B Analyt Technol Biomed Life Sci,2014,951-952:110-118.
[11]Oyaert M,Peersman N,Kieffer D,et al.Novel LC-MS/MS method for plasma vancomycin:comparison with immunoassays and clinical impact[J].Clin Chim Acta,2015,441:63-70.
[12]Ahsman M J,Wildschut E D,Tibboel D,et al.Microanalysis ofβ-lactam antibiotics and vancomycin in plasma for pharmacokinetic studies in neonates[J].Antimicrob Agents Chemother,2009,53(1):75-80.
[13]Zhang T,Watson D G,Azike C,et al.Determination of vancomycin in serum by liquid chromatography-high resolution full scan mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,857(2):352-356.
[14]程晓亮,尤海生,王茂义,等.LC-MS/MS法同时测定人血浆中紫杉醇和多西他赛的质量浓度[J].西北药学杂志,2017,32(5):580-584.
[15]Wu X J,Zhang J,Yu J C,et al.Establishment of norvancomycin fluorescence polarization immunoassay for therapeutic drug monitoring[J].J Antibiot,2012,65(1),35-39.
[16]Matuszewski B K,Constanzer M L,Chavez-Eng C M.Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS[J].Anal Chem,2003,75(1):3019-3030.
[17]Jiang H L,Cao H C,Zhang Y,et al.Systematic evaluation of supported liquid extraction in reducing matrix effect and improving extraction efficiency in LC-MS/MS based bioanalysis for 10 model pharmaceutical compounds[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,891-892:71-80.
[18]Ismaiel O A,Zhang T Y,Jenkins R G,et al.Investigation of endogenous blood plasma phospholipids,cholesterol and glycerides that contribute to matrix effects in bioanalysis by liquid chromatography/mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2010,878(31):3303-3316.
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