title: Quantification and validation of ertapenem using a liquid chromatography-tandem mass spectrometry method.
abstract: Ertapenem, a carbapenem, relies on time-dependent killing. Therapeutic drug monitoring (TDM) should be considered, when ertapenem is used in specific populations, to achieve optimal bactericidal activity and optimize drug-dosing regimens. No validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been reported using deuterated ertapenem as the internal standard. A new simple and robust LC-MS/MS method using a quadrupole mass spectrometer was developed for analysis of ertapenem in human plasma, using deuterated ertapenem as the internal standard. The calibration curve was linear over a range of 0.1 (lower limit of quantification [LLOQ]) to 125 mg/liter. The calculated accuracy ranged from -2.4% to 10.3%. Within-run coefficients of variation (CV) ranged from 2.7% to 11.8%, and between-run CV ranged from 0% to 8.4%. Freeze-thaw stability had a bias of -3.3% and 0.1%. Storage of QC samples for 96 h at 4°C had a bias of -4.3 to 5.6%, storage at room temperature for 24 h had a bias of -10.7% to -14.8%, and storage in the autosampler had a bias between -2.9% and -10.0%. A simple LC-MS/MS method to quantify ertapenem in human plasma using deuterated ertapenem as the internal standard has been validated. This method can be used in pharmacokinetic studies and in clinical studies by performing TDM.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: S P
authors.initials: SP
authors.lastname: van Rijn
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: A M A
authors.initials: AM
authors.lastname: Wessels
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Greijdanus
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands j.w.c.alffenaar@umcg.nl.
authors.forename: J W C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D000077727:Ertapenem; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D047090:beta-Lactams / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem
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