Stability of meropenem in plasma versus dried blood spots (DBS)

Abstract

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 D6-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.