Teaching a New Dog Old Tricks: Ultrafast Liquid Chromatography/Tandem-Mass Spectrometry Analysis of Nine ß-Lactam Antibiotics for Improved Therapeutic Drug Monitoring. Issue 6 (December 2022)

• Record Type: Journal Article
• Authors: Hodgkins, Christopher; Cordwell, Stuart J.; Kocic, Danijela
• Is Part Of: Therapeutic drug monitoring. Volume 44:Issue 6(2022)
• Page Start: 777
• Page End: 783
• Publication Date: 2022-12
• Subjects: therapeutic drug monitoring -- LC/MS -- antibiotic -- high-performance liquid chromatography -- mass spectrometry; Pharmacokinetics -- Periodicals; Patient monitoring -- Periodicals; Drugs -- Analysis -- Periodicals; Body fluids -- Analysis -- Periodicals; Drug Therapy -- Periodicals; Monitoring, Physiologic -- Periodicals; Pharmacology -- Periodicals; 615.7
• DOI: 10.1097/FTD.0000000000001007
• Languages: English
• ISSNs: 0163-4356

Abstract

Abstract : Supplemental Digital Content is Available in the Text. Abstract : Background: Therapeutic drug monitoring (TDM) of β-lactam antibiotics provides critical knowledge in hospital intensive care unit environments to support dosing within the narrow window between therapeutic failure and toxicity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the most suitable analytical technique for these drugs; however, clinicians, patients, and laboratories would benefit from shortening the timeframe between the collection of samples and reporting of results. Methods: The authors developed a very rapid LC-MS/MS method for 9 β-lactam antimicrobial drugs on a commercial core–shell reverse-phase LC column by exploiting the performance of such stationary phase materials at a high mobile-phase linear velocity and using a simple flow split to optimize ionization conditions in the mass spectrometer ion source. The method's performance was assessed using a currently validated routine LC-MS/MS assay performed on the same instrument. Results: Routine ß-lactam assays were reduced from >6 minutes per sample to less than 2 minutes with improved chromatographic resolution, while still maintaining acceptable analytical performance (average correlation coefficient: 0.99670, interday imprecision: 2.0%–10.8%, and bias: –1.68%), hence generating results in agreement with an existing validated method for patient and quality assurance program samples. Conclusions: Time-critical results, such as those for β-lactam antimicrobials, may be reported by the TDM laboratory several hours earlier than current methods allow, providing improved patient care and generating capacity on LC-MS/MS instruments for larger batch sizes and/or additional assays. The simple-to-implement technique demonstrated in this study may be applicable to other TDM assays or any LC-MS/MS method where faster turnaround times are desirable.