中枢神经系统感染患儿脑脊液利奈唑胺浓度测定方法初探
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摘要
目的:建立测定利奈唑胺在中枢神经系统感染患儿脑脊液中浓度的高效液相色谱法(HPLC)。方法:采用Syncronis C_(18)柱(5μm,4. 6 mm×250 mm);流动相为乙腈-水(含0. 2%磷酸)=27∶73;流速1. 0 m L/min;检测波长254 nm;柱温30℃。结果:利奈唑胺在脑脊液浓度为0. 2～40. 0μg/m L范围内浓度和峰面积线性关系良好,标准曲线为As=0. 553 9C-0. 019 3(r=0. 999 9,n=5)。最低定量限、低浓度、中浓度、高浓度的日内和日间变异RSD均<9%,准确度范围为99%～112%,提取回收率在85%～107%。稳定性考察RSD<8%。结论:该方法准确性高、灵敏度好且操作简便,适用于监测利奈唑胺在中枢神经系统感染患儿脑脊液中的浓度,进而为利奈唑胺的个体化用药提供参考。
Objective: To establish the high performance liquid chromatography( HPLC) method for determination of linezolid concentration in cerebrospinal fluid of children with central nervous system infection. Methods: Syncronis C_(18) column( 5 μm,4. 6 mm×250 mm) was used,the mobile phase was acetonitrile ∶ water( containing 0. 2% phosphoric acid) = 27 ∶ 73,the flow rate was 1. 0 m L/min,and the detection wavelength was 254 nm,with column temperature of 30 ℃. Results: Linezolid had good linear relationship between concentration and peak area in the range of cerebrospinal fluid concentration of 0. 2 to 40. 0 μg/m L. The standard curve was As = 0. 553 9 C-0. 019 3( r = 0. 999 9,n = 5). The intra-and inter-day variation RSD of the lowest quantitative limit,low concentration,medium concentration and high concentration were all <9%,the accuracy ranged from 99% to 112%,and the extraction recovery rate ranged from 85% to 107%. Stability was investigated for RSD < 8%. Conclusion: The method has higher accuracy,better sensitivity and easier operation,and is suitable for monitoring the concentration of linezolid in the cerebrospinal fluid of children with central nervous system infection,thereby providing basis for the individualized administration of linezolid.
Objective: To establish the high performance liquid chromatography( HPLC) method for determination of linezolid concentration in cerebrospinal fluid of children with central nervous system infection. Methods: Syncronis C_(18) column( 5 μm,4. 6 mm×250 mm) was used,the mobile phase was acetonitrile ∶ water( containing 0. 2% phosphoric acid) = 27 ∶ 73,the flow rate was 1. 0 m L/min,and the detection wavelength was 254 nm,with column temperature of 30 ℃. Results: Linezolid had good linear relationship between concentration and peak area in the range of cerebrospinal fluid concentration of 0. 2 to 40. 0 μg/m L. The standard curve was As = 0. 553 9 C-0. 019 3( r = 0. 999 9,n = 5). The intra-and inter-day variation RSD of the lowest quantitative limit,low concentration,medium concentration and high concentration were all <9%,the accuracy ranged from 99% to 112%,and the extraction recovery rate ranged from 85% to 107%. Stability was investigated for RSD < 8%. Conclusion: The method has higher accuracy,better sensitivity and easier operation,and is suitable for monitoring the concentration of linezolid in the cerebrospinal fluid of children with central nervous system infection,thereby providing basis for the individualized administration of linezolid.
引文
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[3]赵明亮,孙世中,杨细平,等.利奈唑胺治疗14例神经外科术后耐甲氧西林葡萄球菌颅内感染临床分析[J].中国危重病急救医学,2012,24(3):175.
[4]孙纯广,白楠,蔡芸,等. LC-MS/MS法测定血浆中利奈唑胺浓度[J].中国临床药理学杂志,2010(10):772-776.
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[7]张永煌,张善堂,张蕾,等.重症感染患者血清中利奈唑胺的浓度测定与临床应用评价[J].中华医院感染学杂志,2016,26(3):564-567.
[8]KIELSTEIN J,BURKHARDT O. Dosing of antibiotics in critically ill patients undergoing renal replacement therapy[J]. Curr Pharm Biotechnol,2011,12(12):2015-2019.
[9]李淑娟,马彦,张弋.高效液相色谱法测定人脑脊液中利奈唑胺浓度[J].中国医院药学杂志,2012,32(10):785-787.
[10]李春杏,付强,朱珠.高效液相色谱法测定人血清、脑脊液和胰液中利奈唑胺浓度[J].中国药学杂志,2015,50(4):357-361.
[11]蔡艳,张莉,李海燕,等.脑脊液中利奈唑胺质量浓度测定方法的建立及临床应用[J].西北药学杂志,2016,31(6):581-583.
[12]CHAREHSAZ M,GURBAY A,AYDIN A,et al. Simple,fast and reliable liquid chromatographic and spectrophotometric methods for the determination of theophylline in urine,saliva and plasma samples[J]. Iran J Pharm Res,2014,13(2):431-439.
[13]中华医学会检验医学分会,卫生计生委临床检验中心.液相色谱-质谱临床应用建议[J].中华检验医学杂志,2017,40(10):770.
[14]李淑娟,马彦,张国斌,等.利奈唑胺在脑膜炎患者脑脊液中的药动学及药效学研究[J].中国药房,2015,26(17):2339-2341.
[2]ADEMBRI C,FALLANI S,CASSETTA M I,et al. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septicpa-tientis:Intermittent versus continuous infusion[J]. Int J Antimicrob Agents,2008,31(2):122-129.
[3]赵明亮,孙世中,杨细平,等.利奈唑胺治疗14例神经外科术后耐甲氧西林葡萄球菌颅内感染临床分析[J].中国危重病急救医学,2012,24(3):175.
[4]孙纯广,白楠,蔡芸,等. LC-MS/MS法测定血浆中利奈唑胺浓度[J].中国临床药理学杂志,2010(10):772-776.
[5]TOBIN C M,SUNDERLAND J,WHITE L O,et al. A simple,isocratic high-performance liquid chromatography assay for linezolid in human serum[J]. Journal of antimicrobial chemotherapy,2001,48(5):605-608.
[6]TOUTAIN J,BOSELLI E,DJABAROUTI S,et al. Determination of Linezolid in plasma and bronchoalveolar lavage by highperformance liquid chromatography with ultraviolet detection using a fully automated extraction method[J]. J Chromatogr Analyt Technol Biomed Life Sci,2004,813(1):145-150.
[7]张永煌,张善堂,张蕾,等.重症感染患者血清中利奈唑胺的浓度测定与临床应用评价[J].中华医院感染学杂志,2016,26(3):564-567.
[8]KIELSTEIN J,BURKHARDT O. Dosing of antibiotics in critically ill patients undergoing renal replacement therapy[J]. Curr Pharm Biotechnol,2011,12(12):2015-2019.
[9]李淑娟,马彦,张弋.高效液相色谱法测定人脑脊液中利奈唑胺浓度[J].中国医院药学杂志,2012,32(10):785-787.
[10]李春杏,付强,朱珠.高效液相色谱法测定人血清、脑脊液和胰液中利奈唑胺浓度[J].中国药学杂志,2015,50(4):357-361.
[11]蔡艳,张莉,李海燕,等.脑脊液中利奈唑胺质量浓度测定方法的建立及临床应用[J].西北药学杂志,2016,31(6):581-583.
[12]CHAREHSAZ M,GURBAY A,AYDIN A,et al. Simple,fast and reliable liquid chromatographic and spectrophotometric methods for the determination of theophylline in urine,saliva and plasma samples[J]. Iran J Pharm Res,2014,13(2):431-439.
[13]中华医学会检验医学分会,卫生计生委临床检验中心.液相色谱-质谱临床应用建议[J].中华检验医学杂志,2017,40(10):770.
[14]李淑娟,马彦,张国斌,等.利奈唑胺在脑膜炎患者脑脊液中的药动学及药效学研究[J].中国药房,2015,26(17):2339-2341.