Determination of avibactam and ceftazidime in human plasma samples by LC–MS. (July 2015)

• Record Type: Journal Article
• Authors: Sillén, Henrik; Mitchell, Richard; Sleigh, Rebecca; Mainwaring, Guy; Catton, Katherine; Houghton, Richard; Glendining, Karen
• Is Part Of: Bioanalysis. Volume 7:Number 12(2015)
• Page Start: 1423
• Page End: 1434
• Publication Date: 2015-07
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.15.76
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: Avibactam, a novel non-β-lactam β-lactamase inhibitor co-administrated with the β-lactam antibiotic ceftazidime, is in clinical development. The need to evaluate its PK and PD requires accurate and reliable bioanalytical methods.Methods: We describe LC–MS/MS methods for the determination of avibactam and ceftazidime in human plasma. Avibactam was extracted using weak anionic exchange solid-phase extraction and analyzed on an amide column. Ceftazidime was extracted using protein precipitation and analyzed on a C18 column. Calibration curves were established over 10–10, 000 ng/ml (avibactam) and 43.8–87, 000 ng/ml (ceftazidime).Results & conclusion: Method validation, cross-validation between three laboratories and incurred sample re-analysis demonstrated method robustness. The methods were successfully applied to multiple clinical studies.