UPLC法测定患者美罗培南的血药浓度
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摘要
目的建立超高效液相色谱法测定人血浆中美罗培南的方法,并用该法对临床使用美罗培南的患者进行血药浓度测定。方法色谱柱为Zorbax Eclipse Plus C_(18)柱(2.1mm×100mm,1.8μm),流动相为乙腈-0.01mol·L~(-1)磷酸二氢钾缓冲液(6.3∶93.7,V/V),流速:0.4ml·min~(-1),柱温:30℃,检测波长:299nm,内标为甲硝唑。结果美罗培南与血浆中其它组分分离良好,线性范围为0.5~80.0μg·ml~(-1),日内和日间RSD均小于10%,美罗培南平均提取回收率为82.2%,方法平均回收率为101.9%。测定10例患者美罗培南谷浓度范围为0.73~32.30μg·ml~(-1),浓度值差异较大,其中3例患者的血药谷浓度低于4.0μg·ml~(-1)。结论该方法快速、灵敏、准确,适用于美罗培南临床血药浓度监测。临床患者美罗培南的谷浓度差异较大,测定患者美罗培南的血药浓度对促进美罗培南在临床合理应用具有重要意义。
Objective To establish a UPLC method for determining the meropenem concentration in human plasma and to apply this method to patients.Methods The samples were analyzed by an Agilent 1290 UPLC system with a Zorbax Eclipse Plus C_(18) column(2.1 mm×100 mm,1.8μm)at 30℃at a flow rate of 0.4 ml·min~(-1),and UV detection wavelength of 299 nm.The mobile phase was acetonitrile-0.01 mol·L~(-1) KH_2PO_4(40∶60,V/V).Results The calibration curve was linear within the range of 0.5-80.0μg·ml~(-1) using a 0.2 ml sample volume.The intra-and inter-day precisions were both below 10%.The extraction and recovery rates were 82.2% and 101.9%,respectively.The individual variability of meropenem trough concentrations was high among the 10 patients,ranging from 0.73μg·ml~(-1) to 32.30μg·ml~(-1),while the concentrations in 3 patients were much lower than 4.0μg·ml~(-1).Conclusion This UPLC method is sensitive,quick and accurate,which can be used for therapeutic drug monitoring(TDM)of meropenem.Determination of meropenem concentrations in patients′plasma is necessary.
Objective To establish a UPLC method for determining the meropenem concentration in human plasma and to apply this method to patients.Methods The samples were analyzed by an Agilent 1290 UPLC system with a Zorbax Eclipse Plus C_(18) column(2.1 mm×100 mm,1.8μm)at 30℃at a flow rate of 0.4 ml·min~(-1),and UV detection wavelength of 299 nm.The mobile phase was acetonitrile-0.01 mol·L~(-1) KH_2PO_4(40∶60,V/V).Results The calibration curve was linear within the range of 0.5-80.0μg·ml~(-1) using a 0.2 ml sample volume.The intra-and inter-day precisions were both below 10%.The extraction and recovery rates were 82.2% and 101.9%,respectively.The individual variability of meropenem trough concentrations was high among the 10 patients,ranging from 0.73μg·ml~(-1) to 32.30μg·ml~(-1),while the concentrations in 3 patients were much lower than 4.0μg·ml~(-1).Conclusion This UPLC method is sensitive,quick and accurate,which can be used for therapeutic drug monitoring(TDM)of meropenem.Determination of meropenem concentrations in patients′plasma is necessary.
引文
[1]林立敏,张晶,宋洪涛.美罗培南在特殊机体状态下的PK/PD及给药方案研究进展[J].中国抗生素杂志,2015,40(4):309-317
[2]徐兵,杨阳,周广青,等.基于T>MIC的美罗培南的给药方案建立[J].中国医院药学杂志,2014,34(1):69-73
[3]张红,金路,葛卫红,等.不同生理病理状态下美罗培南药动学/药效学差异性研究进展[J].中国感染与化疗杂志,2016,16(1):92-98
[4]孔维华,鞠浩爽,王晓雪,等.HPLC测定人血浆中亚胺培南、美罗培南、帕尼培南、法罗培南浓度[J].中国药学杂志,2014,49(14):1247-1251
[5]任秋霞,刘淼,吴荣荣,等.UPLC法测定人血浆中丙泊酚含量[J].解放军药学学报,2014,30(6):541-543
[6]冯锦华.高效液相色谱法检测老年ICU患者血清美罗培南的浓度及药代动力学变化[J].中国老年学杂志,2014,34(20):5864-5865
[7]Roth T,Fiedler S,Mihai S,et al.Determination of meropenem levels in human serum by high-performance liquid chromatography with ultraviolet detection[J].Biomed Chromatogr,2017,31(5):1-7
[8]杨阳,李昕,徐兵,等.反相高效液相色谱法测定美罗培南的血药浓度及其临床应用[J].中南药学,2014,12(8):761-764
[9]Troger U,Drust A,Martens-Lobenhoffer J,et al.Decreased meropenem levels in Intensive Care Unit patients with augmented renal clearance:benefit of therapeutic drug monitoring[J].Int J Antimicrob Ag,2012,40(4):370-372
[2]徐兵,杨阳,周广青,等.基于T>MIC的美罗培南的给药方案建立[J].中国医院药学杂志,2014,34(1):69-73
[3]张红,金路,葛卫红,等.不同生理病理状态下美罗培南药动学/药效学差异性研究进展[J].中国感染与化疗杂志,2016,16(1):92-98
[4]孔维华,鞠浩爽,王晓雪,等.HPLC测定人血浆中亚胺培南、美罗培南、帕尼培南、法罗培南浓度[J].中国药学杂志,2014,49(14):1247-1251
[5]任秋霞,刘淼,吴荣荣,等.UPLC法测定人血浆中丙泊酚含量[J].解放军药学学报,2014,30(6):541-543
[6]冯锦华.高效液相色谱法检测老年ICU患者血清美罗培南的浓度及药代动力学变化[J].中国老年学杂志,2014,34(20):5864-5865
[7]Roth T,Fiedler S,Mihai S,et al.Determination of meropenem levels in human serum by high-performance liquid chromatography with ultraviolet detection[J].Biomed Chromatogr,2017,31(5):1-7
[8]杨阳,李昕,徐兵,等.反相高效液相色谱法测定美罗培南的血药浓度及其临床应用[J].中南药学,2014,12(8):761-764
[9]Troger U,Drust A,Martens-Lobenhoffer J,et al.Decreased meropenem levels in Intensive Care Unit patients with augmented renal clearance:benefit of therapeutic drug monitoring[J].Int J Antimicrob Ag,2012,40(4):370-372