Therapeutic drug monitoring of beta-lactam antibiotics

• Verfasst von: Pinder, Nadine [VerfasserIn]
• Verfasst von: Brenner, Thorsten [VerfasserIn]
• Verfasst von: Swoboda, Stefanie [VerfasserIn]
• Verfasst von: Weigand, Markus A. [VerfasserIn]
• Verfasst von: Hoppe-Tichy, Torsten [VerfasserIn]
• Titel: Therapeutic drug monitoring of beta-lactam antibiotics
• Titelzusatz: influence of sample stability on the analysis of piperacillin, meropenem, ceftazidime and flucloxacillin by HPLC-UV
• Verf.angabe: Nadine Pinder, Thorsten Brenner, Stefanie Swoboda, Markus A. Weigand, Torsten Hoppe-Tichy
• E-Jahr: 2017
• Jahr: 22 May 2017
• Umfang: 8 S.
• Fussnoten: Gesehen am 02.10.2018
• Titel Quelle: Enthalten in: Journal of pharmaceutical and biomedical analysis
• Ort Quelle: New York, NY [u.a.] : Science Direct, 1983
• Jahr Quelle: 2017
• Band/Heft Quelle: 143(2017), Seite 86-93
• ISSN Quelle: 1873-264X
• DOI: doi:10.1016/j.jpba.2017.05.037
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Continuous infusion
• Sach-SW: High performance liquid chromatography
• Sach-SW: Plasma concentrations
• Sach-SW: Pre-analytical stability
• Sach-SW: S-Monovette Lithium-Heparin gel
• Sach-SW: Whole blood
• K10plus-PPN: 1581507968

Abstract

Introduction Therapeutic drug monitoring (TDM) is a useful tool to optimize antibiotic therapy. Increasing interest in alternative dosing strategies of beta-lactam antibiotics, e.g. continuous or prolonged infusion, require a feasible analytical method for quantification of these antimicrobial agents. However, pre-analytical issues including sample handling and stability are to be considered to provide valuable analytical results. Methods for the simultaneous determination of piperacillin, meropenem, ceftazidime and flucloxacillin, a high performance liquid chromatography (HPLC) method including protein precipitation was established utilizing ertapenem as internal standard. Long-term stability of stock solutions and plasma samples were monitored. Furthermore, whole blood stability of the analytes in heparinized blood tubes was investigated comparing storage under ambient conditions and 2-8°C. Results A calibration range of 5-200μg/ml (piperacillin, ceftazidime, flucloxacillin) and 2-200μg/ml (meropenem) was linear with r2>0.999, precision and inaccuracy were <9% and <11%, respectively. The successfully validated HPLC assay was applied to clinical samples and stability investigations. At −80°C, plasma samples were stable for 9 months (piperacillin, meropenem) or 13 months (ceftazidime, flucloxacillin). Concentrations of the four beta-lactam antibiotics in whole blood tubes were found to remain within specifications for 8h when stored at 2-8°C but not at room temperature. Conclusions The presented method is a rapid and simple option for routine TDM of piperacillin, meropenem, ceftazidime and flucloxacillin. Whereas long-term storage of beta-lactam samples at −80°C is possible for at least 9 months, whole blood tubes are recommended to be kept refrigerated until analysis.