Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
J Pharm Biomed Anal. 2019 Jun 5;170:279-284. doi: 10.1016/j.jpba.2019.03.055. Epub 2019 Mar 25.
Meropenem, a beta-lactam antibiotic belonging to the group of carbapenems, is widely used in the treatment of serious and complicated infections. Therapeutic drug monitoring (TDM) is strongly recommended to achieve therapeutic success, but the limited stability of the drug in plasma makes transport between clinic and laboratory difficult. The aim of this study was to investigate whether the stability of meropenem was improved in dried blood spots (DBS) and whether sample transport between clinic and laboratory could be simplified by using this medium. Meropenem was quantified in DBS punch-out discs after extraction into acetonitrile - water (70:30 v:v) containing the internal standard D-meropenem. The extracts were analyzed by hydrophilic interaction liquid chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS). The calibration function was linear in the range of 0.5-50 μg/mL. Intra-day coefficients of variation were better than 12% with accuracies better than 5%. The corresponding inter-day values were better than 7% and 6%, respectively. Meropenem was stable for at least 7 days on DBS at -20 °C and 6 °C, whereas in plasma at 6 °C, meropenem showed a decay of <15% in 4 d. Stored at 23 °C, loss of <15% were observed during 11 h in plasma and about 48 h in DBS, allowing for DBS sample transport by mail. A pilot study with intensive care patients receiving meropenem (n = 33) showed that, after correction for hematocrit, plasma concentrations can be successfully calculated from the DBS quantification results, making DBS potentially applicable for TDM purposes.
美罗培南是一种属于碳青霉烯类的β-内酰胺类抗生素，广泛用于治疗严重和复杂的感染。强烈建议进行治疗药物监测（TDM）以获得治疗成功，但药物在血浆中的有限稳定性使得在临床和实验室之间的运输变得困难。本研究旨在探讨美罗培南在干血斑（DBS）中的稳定性是否得到改善，以及是否可以通过使用这种介质简化临床和实验室之间的样本运输。用含有内标 D-美罗培南的乙腈-水（70:30v:v）从 DBS 打孔盘提取后，在 DBS 打孔盘提取后对美罗培南进行定量。采用亲水作用液相色谱（HILIC）与串联质谱（MS/MS）联用对提取物进行分析。校准函数在 0.5-50μg/mL 范围内呈线性。日内变异系数优于 12%，准确度优于 5%。相应的日间值分别优于 7%和 6%。美罗培南在-20°C 和 6°C 的 DBS 中至少稳定 7 天，而在 6°C 的血浆中，美罗培南在 4 天内降解<15%。在 23°C 下储存时，在血浆中观察到<15%的损失持续 11 小时，在 DBS 中约 48 小时，允许通过邮件运输 DBS 样本。一项对接受美罗培南治疗的重症监护患者进行的初步研究（n=33）表明，在对红细胞压积进行校正后，可从 DBS 定量结果成功计算出血浆浓度，这使得 DBS 有可能适用于 TDM 目的。
