PDF(Pubmed)
Abstract：
Meropenem is an ultrabroad-spectrum antimicrobial agent that is often recommended for the treatment of bacterial meningitis (BM) in children. However, a subtherapeutic phenomenon occurred in BM children complicated with augmented renal clearance (ARC) at the recommended dose of meropenem. To support its pharmacokinetics, a sensitive, fast and robust ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to measure meropenem concentrations in serum and cerebrospinal fluid (CSF). The method involved protein precipitation, and samples were diluted with a large proportion of water to eliminate solvent effects. The separation of samples was performed on a Waters Acquity™ BEH C18 column (2.1 × 50 mm i.d., 1.7 μm) with a gradient profile. The mobile phases were formic acid-water (1:1000, v/v) and acetonitrile. The linear range was good, with a concentration range of 0.100-100 μg/mL for serum and 0.0400-20.0 μg/mL for CSF. The intra-day and inter-day precisions were less than 8.0%, and the intra-day and inter-day accuracies varied -6.6% from 6.5% for the both serum and CSF. The selectivity, carry-over, dilution integrity, matrix effect, recovery and stability were validated according to international guidelines. The developed UPLC-MS/MS method successfully determined the meropenem concentrations in the serum and CSF of children with BM complicated with ARC. The results indicated that under the recommended dosing regimen (40 mg/kg every 8 h), the time to reach the effective treatment target of 50%T > MIC was only approximately 3 h and lower CSF concentrations of meropenem were observed in children with BM with ARC.
摘要：
美罗培南是一种超广谱抗微生物剂，通常被推荐用于治疗儿童细菌性脑膜炎（BM）。然而,在推荐剂量的美罗培南下,BM患儿出现亚治疗现象,并发肾脏清除率(ARC)增强.为了支持其药代动力学，一个敏感的,建立了快速可靠的超液相色谱-串联质谱（UPLC-MS/MS）方法，用于测量血清和脑脊液（CSF）中的美罗培南浓度。该方法涉及蛋白沉淀，和样品用大比例的水稀释以消除溶剂的影响。样品的分离在WatersAcquity™BEHC18色谱柱(2.1×50mm内径,1.7μm）具有梯度轮廓。流动相为甲酸-水(1:1000,v/v)和乙腈。线性范围较好,血清浓度范围为0.100-100μg/mL，CSF浓度范围为0.0400-20.0μg/mL。日内和日间精确度低于8.0%，血清和CSF的日内和日间准确度从6.5％变化为-6.6％。选择性,结转,稀释完整性，基体效应，根据国际指南验证了回收率和稳定性.建立的UPLC-MS/MS方法成功地测定了BM合并ARC患儿血清和CSF中美罗培南的浓度。结果表明，在推荐的给药方案下（每8小时40mg/kg），达到50%T>MIC的有效治疗目标的时间仅约3小时,并且在有ARC的BM患儿中观察到较低的美罗培南CSF浓度.
