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引用本文:陈灵,郭婷,邵钰,边俊梅,吴金虎.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[J].中国现代应用药学,2023,40(22):3158-3163.
CHEN Ling,GUO Ting,SHAO Yu,BIAN Junmei,WU Jinhu.Determination of Flucloxacillin Concentration in Newborn Plasma by HPLC-MS/MS and the Study on the Interaction with Ambroxol[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(22):3158-3163.
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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
陈灵1, 郭婷2, 邵钰3, 边俊梅4, 吴金虎1
1.武汉市第三医院(武汉大学附属同仁医院), 药学部, 武汉 430060;2.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;3.北京市昌平区中医医院药学部, 北京 102200;4.武汉市第三医院(武汉大学附属同仁医院), 儿科, 武汉 430060
摘要:
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API4000 HPLC-MS/MS进行分析,色谱柱为Ultimate XB-C18(2.1 mm×100 mm,5 μm),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0.20~80 ng·mL-1,定量下限为0.20 ng·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。
关键词:  氟氯西林  氨溴索  药物-药物相互作用  HPLC-MS/MS
DOI:10.13748/j.cnki.issn1007-7693.20231774
分类号:R917.101
基金项目:湖北省中央引导地方科技发展专项(2020ZYYD026);湖北省卫生健康委员会科研项目(WJ2021M011)
Determination of Flucloxacillin Concentration in Newborn Plasma by HPLC-MS/MS and the Study on the Interaction with Ambroxol
CHEN Ling1, GUO Ting2, SHAO Yu3, BIAN Junmei4, WU Jinhu1
1.Wuhan Third Hospital(Tongren Hospital of Wuhan University), Department of Pharmacy, Wuhan 430060, China;2.Department of Pharmacy, Bishan Hospital of Chongqing Medical University(Bishan Hospital of Chongqing), Chongqing 402760, China;3.Department of Pharmacy, Changping Hospital of Traditional Chinese Medicine, Beijing 102200, China;4.Wuhan Third Hospital(Tongren Hospital of Wuhan University), Department of Paediatrics, Wuhan 430060, China
Abstract:
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×100 mm, 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 m/z 821.4→397.3 for rifampicin(internal 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.
Key words:  flucloxacillin  ambroxol  drug-drug interaction  HPLC-MS/MS
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