首页|HPLC-MS/MS测定新生儿血浆中氟氯西林的浓度及其与氨溴索相互作用的研究

HPLC-MS/MS测定新生儿血浆中氟氯西林的浓度及其与氨溴索相互作用的研究

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目的 建立一种高效、简便的HPLC-MS/MS方法检测新生儿血浆中氟氯西林的浓度,研究新生儿体内氨溴索与氟氯西林是否存在相互作用.方法 生物样本采用API4000HPLC-MS/MS进行分析,色谱柱为Ultimate XB-C18(2.1 mm×100mm,5μm),流动相A相为水-0.1%甲酸,B相为乙腈-0.1%甲酸.氟氯西林和内标利福平定量分析离子对分别为m/z 452.6→284.2和m/z 821.4-397.3.结果 在该分析方法下氟氯西林的线性范围为0.20~80ng·mL-1,定量下限为0.20ng·mL-1;氟氯西林的日内精密度和日间精密度均<8.23%;提取回收率为85.3%~89.2%,基质效应为89.3%~92.3%;新生儿血浆样品在室温条件下放置12 h,处理后室温条件下放置4 h,反复冻融3次及-20 ℃冷冻30 d的稳定性均良好.临床样本检测结果表明氨溴索合用可以显著提高氟氯西林血药浓度.结论 本研究所建立的HPLC-MS/MS分析方法准确度高,灵敏度好,可用于新生儿血浆中氟氯西林浓度的测定.临床研究结果表明氨溴索能显著提升氟氯西林的血药浓度,两者存在药物相互作用.
Determination of Flucloxacillin Concentration in Newborn Plasma by HPLC-MS/MS and the Study on the Interaction with Ambroxol
OBJECTIVE To establish an efficient and simple HPLC-MS/MS method for determination of flucloxacillin in newborn plasma,and to investigate the interaction between ambroxol and flucloxacillin in newborns.METHODS The samples were analyzed by API4000 HPLC-MS/MS.Ultimate XB-C18 column(2.1 mm×100mm,5 μm)were carried out.The mobile phase was composed of water-0.1%formic acid(A)and acetonitrile-0.1%formic acid(B).The quantitative analysis of the ion transitions were monitored at m/z 452.6→284.2 for flucloxacillin and mlz 821.4→397.3 for rifampicin(intemal standard).RESULTS The linear range of flucloxacillin under this analysis method was 0.20-80 ng·mL-1,and the lower limit of quantification was 0.20 ng·mL-1;The intra-day and inter-day precision of flucloxacillin were both less than 8.23%;The extraction recovery was in the range of 85.3%-89.2%,and the matrix effect was between 89.3%-92.3%;The stability of plasma samples was good under conditions of 12 h at room temperature,4 h at room temperature after treatment,repeated freeze-thaw for 3 times,and-20 ℃ freezing for 30 d.The results of clinical samples indicated that the combination of ambroxol could significantly increase the blood concentration of flucloxacillin.CONCLUSION The established HPLC-MS/MS method is accurate,sensitive and can be used for the determination of flucloxacillin concentration in neonatal plasma.The results of clinical samples indicate that ambroxol can significantly increase the blood concentration of flucloxacillin.There are drug interactions between ambroxol and flucloxacillin.

flucloxacillinambroxoldrug-drug interactionHPLC-MS/MS

陈灵、郭婷、邵钰、边俊梅、吴金虎

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武汉市第三医院(武汉大学附属同仁医院)药学部,武汉 430060

重庆医科大学附属璧山医院(重庆市璧山区人民医院)药学部,重庆 402760

北京市昌平区中医医院药学部,北京 102200

武汉市第三医院(武汉大学附属同仁医院)儿科,武汉 430060

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氟氯西林 氨溴索 药物-药物相互作用 HPLC-MS/MS

湖北省中央引导地方科技发展专项湖北省卫生健康委科研项目

2020ZYYD026WJ2021M011

2023

中国现代应用药学
中国药学会

中国现代应用药学

CSTPCDCSCD北大核心
影响因子:0.877
ISSN:1007-7693
年,卷(期):2023.40(22)
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