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Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma.

ABSTRACT: A parenteral medical combination containing vaborbactam and meropenem is used mainly to treat complicated urinary tract infections. A novel ultra-performance liquid chromatography tandem mass spectrometric method was developed for the sensitive determination of both compounds in human plasma. Sample preparation was performed by precipitation technique. The chromatographic separation was accomplished using the Acquity C18-BEH column, 0.01 M ammonium formate: acetonitrile (47 : 53, v/v) as a mobile phase with a flow rate of 0.2 ml min-1. Analytes were monitored by applying multiple reaction monitoring. The bioanalytical validation criteria were conducted following the Food and Drug Administration recommendations. The method was linear within range 0.5 to 50 µg ml-1, for both drugs. The intra-day and inter-day precision, as coefficient variation (% CV) and the accuracy, as % bias did not exceed 15% for both drugs. The percentage recovery of targeted analytes was not less than 77%, calculated at three quality control levels. The proposed method showed a suitable lower level of quantification value of 0.50 µg ml-1 for both analytes, which is far lower than the expected C max, which permits the use of this method for pharmacokinetic studies. The proposed method proved to be useful for the evaluation of this combination in both human plasma and pharmaceutical formulation.

SUBMITTER: Kammoun AK

PROVIDER: S-EPMC7428257 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma.

Kammoun Ahmed K AK Khedr Alaa A Khayyat Ahdab N AN Hegazy Maha A MA

Royal Society open science 20200708 7

A parenteral medical combination containing vaborbactam and meropenem is used mainly to treat complicated urinary tract infections. A novel ultra-performance liquid chromatography tandem mass spectrometric method was developed for the sensitive determination of both compounds in human plasma. Sample preparation was performed by precipitation technique. The chromatographic separation was accomplished using the Acquity C18-BEH column, 0.01 M ammonium formate: acetonitrile (47 : 53, v/v) as a mobil ...[more]

PMID: 32874656

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Project description:Carbapenem-resistant gram-negative pathogens remain an urgent public health threat, and safe, effective treatment options are limited. Although several agents are now available to combat these infections, meropenem-vaborbactam was the first to combine a novel, cyclic, boronic acid-based, β-lactamase inhibitor with a carbapenem backbone. Vaborbactam emanated from a discovery program specifically designed to identify candidate β-lactamase inhibitors with biochemical, microbiologic, and pharmacologic properties optimized for use in conjunction with a carbapenem. Meropenem was selected as the ideal carbapenem given its broad-spectrum in vitro activity, well established safety profile, and proven efficacy in the treatment of serious gram-negative infections. The combination has demonstrated potent in vitro activity against resistant gram-negative pathogens, particularly KPC-producing Klebsiella pneumoniae (MIC50 values typically ≤ 0.06 mg/l). Importantly, the pharmacokinetic (PK) profiles of the two agents are well matched, and the approved optimized dosing regimen of 4 g every 8 h (Q8h) as a 3-h infusion provides reliable probability of target attainment against the majority of commonly encountered carbapenem-resistant Enterobacteriaceae (CRE). Robust in vitro and in vivo PK/pharmacodynamic (PD) data support the ability of this dosing regimen to achieve specified PK/PD targets for both bactericidal activity and prevention of resistance among pathogens with MICs up to 8 mg/l. This concerted effort into optimizing the PK and PD parameters of both the β-lactam and β-lactamase inhibitor alone and in combination contributed to the clinical success of meropenem-vaborbactam demonstrated in phase 3 trials in patients with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), and serious CRE infections. As the use of meropenem-vaborbactam increases concomitantly with the prevalence of KPC-producing CRE, continued pharmacovigilance and antimicrobial stewardship efforts will be of upmost importance to ensure that these PK/PD efforts translate into improved patient outcomes.

Dataset Information

Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma.

Publications

Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma.

Similar Datasets

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