From Bed to Bench: Pre-analytical Stability of 29 Anti-infective Agents in Plasma and Whole Blood to Improve Accuracy of Therapeutic Drug Monitoring

Sophie Magreault; Dorine Pierredon; Judith Akinotcho-Relouzat; Frédéric Méchaï; Brigitte Lamy; Françoise Jaureguy; Vincent Jullien

doi:10.1097/FTD.0000000000001237

From Bed to Bench: Pre-analytical Stability of 29 Anti-infective Agents in Plasma and Whole Blood to Improve Accuracy of Therapeutic Drug Monitoring

Ther Drug Monit. 2024 Jul 2. doi: 10.1097/FTD.0000000000001237. Online ahead of print.

Authors

Sophie Magreault¹, Dorine Pierredon², Judith Akinotcho-Relouzat², Frédéric Méchaï³, Brigitte Lamy⁴, Françoise Jaureguy⁴, Vincent Jullien¹

Affiliations

¹ Department of Pharmacology, AP-HP, Jean Verdier Hospital, Sorbonne Paris Nord and Sorbonne Paris Cité University, IAME, Bobigny, France.
² Department of Pharmacology, AP-HP, Jean Verdier Hospital, Bondy, France.
³ Department of Infectious Disease, AP-HP, Avicenne Hospital, Sorbonne Paris Nord and Sorbonne Paris Cité University, IAME, Bobigny, France; and.
⁴ Department of Microbiology, AP-HP, Avicenne Hospital, Sorbonne Paris Nord and Sorbonne Paris Cité University, IAME, Bobigny, France.

PMID: 38953703
DOI: 10.1097/FTD.0000000000001237

Abstract

Background: Therapeutic drug monitoring requires a validated assay and appropriate conditions for sample shipment and storage based on the stability of the compound to be analyzed. This study evaluated the stability of 29 antimicrobial compounds in whole blood (WB) and plasma samples under various storage conditions.

Methods: The pre-analytical stability of 22 antibiotics (amoxicillin, aztreonam, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftobiprole, ceftolozane, ceftriaxone, ciprofloxacin, clindamycin, cloxacillin, daptomycin, levofloxacin, linezolid, meropenem, metronidazole, moxifloxacin, piperacillin, sulfamethoxazole, and trimethoprim), 2 beta-lactamase inhibitors (avibactam, tazobactam), and 5 antituberculosis drugs (ethambutol, isoniazid, pyrazinamide, rifabutin, and rifampicin) was assessed by WB for up to 24 hours at room temperature (RT) and 72 hours at +4°C. The stability in plasma was evaluated for up to 6 hours at RT, 24 hours at +4°C, 1 month at -20°C, and 6 months at -80°C.

Results: Concerning WB stability, all investigated compounds were stable for 24 hours at RT, except meropenem and isoniazid, which were stable for 6 hours; however, for 24 hours at +4°C, all the compounds were stable. For storage durations of 48 and 72 hours at +4°C, all compounds were stable, except for ciprofloxacin, cotrimoxazole, and isoniazid. Concerning stability in plasma, all compounds were stable for 6 hours at RT, and all except isoniazid were stable for 24 hours at +4°C. All the tested compounds were stable for 7 days at -20°C, except isoniazid, for which a degradation of approximately 20% was observed. An important degradation was observed for beta-lactam antibiotics after 1 month at -20°C. All compounds were stable at -80°C for 6 months.

Conclusions: The pre-analytical stabilities of several anti-infective compounds was described. The present results can be used to determine the appropriate conditions for shipping and storing samples dedicated to therapeutic drug monitoring of the investigated compounds.