A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection

Briscoe, Scott; McWhinney, Brett; Lipman, Jeffrey; Roberts, Jason A.; Ungerer, Jacobus P.J.

doi:10.1016/j.jchromb.2012.09.016

Cited by 116 publications

(89 citation statements)

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“…For a comprehensive review of advances in the determination of -lactam antibiotics by liquid chromatography using different detector systems, the reader is referred to the paper by Lara et al [44]. In general, a number of HPLC methods with ultraviolet detection are described for -lactams including simultaneous determination of several -lactams [45][46][47][48][49].…”

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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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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“…High free fractions were reported in our study mainly related to hypoalbuminemia, but unbound oxacillin concentrations were determined by ultrafiltration and not by equilibrium dialysis, which is the current standard. However, other studies determined the unbound concentration of ␤-lactams (including flucloxacillin and dicloxacillin) using the ultracentrifugation method, and the stability of our method was checked by repeating the technique several times on the same sample to ensure reliability (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

High-Dose Continuous Oxacillin Infusion Results in Achievement of Pharmacokinetics Targets in Critically Ill Patients with Deep Sternal Wound Infections following Cardiac Surgery

Nesseler

Verdier

Launey

et al. 2014

Antimicrob Agents Chemother

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“…Therefore, with the current limitations the use of immunoassays for antibiotics' TDM is not considered as a priority for further development and efforts have been directed to explore other alternatives such as the use of chromatographic techniques. Consequently, liquid-chromatography (LC) coupled to UV [28,[56][57][58][59], chemiluminescence (CL) [60], electrochemical (EC) [61], and mass spectrometry (MS) [62,63], have been widely/successfully used for the detection of β-lactams. 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).…”

Section: Overview Of Published Analytical Methods Optimized For Theramentioning

confidence: 99%

“…As in the case of critically ill patients very low levels can be anticipated methods that offer higher sensitivity are preferred. Furthermore, the analysis time with conventional detectors is usually lengthier from 10 to 22 min [28,57] which makes them, in terms of the fast delivery of the results, less attractive for routine analysis when compared to LC-MS/MS which can offer analysis time of less than 5 min. There is no doubt that conventional methods are less expensive and can be also suitable for TDM; nevertheless, careful consideration should be made when availability, costs, speed and accuracy come into the play.…”

Section: Overview Of Published Analytical Methods Optimized For Theramentioning

confidence: 99%

“…Consequently, it was recommended to directly measure, instead of estimating, the free unbound concentrations [82]. However, it is worth mentioning that from all the currently published analytical methods only one method used ultracentrifugation for the analysis of free drug concentrations of β-lactam antibiotics [57]. For the time being direct determination of free drug concentration has not been widely adopted in methods intended for TDM and free drug levels estimation does not seem to hinder the successful application of the methods in improving the clinical outcome from the antimicrobial therapy of ICU patients.…”

Section: Sample Treatmentmentioning

confidence: 99%

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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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A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection

Cited by 116 publications

References 11 publications

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

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

High-Dose Continuous Oxacillin Infusion Results in Achievement of Pharmacokinetics Targets in Critically Ill Patients with Deep Sternal Wound Infections following Cardiac Surgery

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

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