Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method

Carlier, Mieke; Stove, Veronique; Roberts, Jason A.; Velde, E. Van de; Waele, Jan J. De; Verstraete, Alain G.

doi:10.1016/j.ijantimicag.2012.06.022

Cited by 87 publications

(64 citation statements)

References 20 publications

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“…24 The lower limit of quantification (LLOQ) was 0.5 mg/L for both compounds and the imprecision was < 15% at all levels. For the first 29 patients, only the piperacillin compound was quantified.…”

Section: Drug and Biochemical Assaysmentioning

confidence: 91%

Dose optimization of piperacillin/tazobactam in critically ill children

Cock¹,

Dijkman

Jaeger

et al. 2017

Journal of Antimicrobial Chemotherapy

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Running title: Paediatric piperacillin/tazobactam dose rationale SynopsisObjectives. The aim of this study was to characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.Patients and Methods. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg q6h based on piperacillin). Piperacillin/tazobactam concentrations were measured by a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic data was analysed using nonlinear mixed effects modelling.Results. Piperacillin and tazobactam blood samples were collected from 47 patients (median age: 2.83 years; range: 2 months -15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model which included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 L/h and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) q4h over 2 hours, 100 mg/kg q4h given over 1 hour or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24h were minimally required to achieve the therapeutic targets for piperacillin (60 % fT>MIC>16 mg/L). Conclusion. Standard intermittent dosing regimens do not ensure optimalpiperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.

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Section: Drug and Biochemical Assaysmentioning

confidence: 91%

Dose optimization of piperacillin/tazobactam in critically ill children

Cock¹,

Dijkman

Jaeger

et al. 2017

Journal of Antimicrobial Chemotherapy

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“…Liquid chromatography tandem mass spectrometry (LCMSMS) methods have also been described [50][51][52][53].The use of mass spectroscopy detectors allows a more definitive identification and quantitative determination of compounds, even with low resolution chromatography; a future not possible with other methods of HPLC detection [54]. LCMSMS Page 9 of 48 A c c e p t e d M a n u s c r i p t 9 also offers short time of analysis and is generally regarded as superior to HPLC methods because risk of false positive results is minimal.…”

Section: Page 8 Of 48mentioning

confidence: 99%

“…Two of these, cefotaxime and deacetylecefotaxime, are not commonly used in intensive care units and thus are less relevant as far as application to TDM is concerned. The method by Carlier et al [52]can analyse 7 beta-lactams but does not include bezylpenicillin and ertapenem which were of interest in our TDM program.…”

Section: Page 8 Of 48mentioning

confidence: 99%

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

Sime

Roberts

et al. 2014

Journal of Chromatography B

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThere is strong evidence in literature supporting the benefit of monitoring plasma concentrations of -lactam antibiotics in the critically ill to ensure appropriateness of dosing.The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6µm, 2.1* 50 mm) via gradient elution using water and acetonitrile, each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95%-107% and 95%-108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12 % and 5-14% respectively. The lower limit of quantification was 0.1g/mL for each antibiotic except flucloxacillin (0.25g/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected -lactam antibiotics.Page 5 Highlights  We present a method for simultaneous determination of seven beta-lactams in plasma  The selected antibiotics are those commonly used in critically ill patients  The method is accurate, precise and meets validation requirements by guidelines  It proved applicable for therapeutic drug monitoring and pharmacokinetic studies

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“…Although as compared to mass spectrometry less sophisticated analysis is performed with the use of the other conventional detectors, the speed and sensitivity of the former one surpass those offered by the latter ones (UV, CL, EC). The current interest focuses on LC-MS/MS [60,[64][65][66][67][68][69][70][71][72][73][74]. This is not surprising as it is well acknowledged that LC-MS/ MS has the power of combining the sensitivity of tandem MS and the selectivity of chromatography thus improving the accuracy of quantitating low drug concentrations from different matrices.…”

Section: Overview Of Published Analytical Methods Optimized For Theramentioning

confidence: 99%

“…Although different analytical methods have been developed for the quantification of individual antibiotics, in the last 5 years several methods have been published for the simultaneous analysis of subsets of antibiotics usually given to critically ill patients [64][65][66][67][68][69][70][71][72]74], and continuous attempts for improved method development are ongoing. This stems from the need for rapid and accurate methods for the detection in one run of as many as possible of the antibiotics used as first and second lines of treatment in critically ill patients.…”

Section: Lc-ms/ms For Antibiotics Therapeutic Monitoring What Shall Wmentioning

confidence: 99%

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

El‐Najjar

Gessner

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

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Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method

Cited by 87 publications

References 20 publications

Dose optimization of piperacillin/tazobactam in critically ill children

Dose optimization of piperacillin/tazobactam in critically ill children

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

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