Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure

Joost J. van Raaij; Noortje J. D. Mabelis; Kimberly N. Shudofsky; Sjoerd D. Meenks; Jos L. M. L. le Noble; Paddy K. C. Janssen

doi:10.1002/jcla.23100

Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure

Joost J. van Raaij, Noortje J. D. Mabelis, Kimberly N. Shudofsky, Sjoerd D. Meenks, Jos L. M. L. le Noble, Paddy K. C. Janssen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. Methods Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). Results Intra-assay and inter-assay precision was

Original language	English
Article number	23100
Number of pages	7
Journal	Journal of Clinical Laboratory Analysis
Volume	34
Issue number	3
Early online date	30 Nov 2019
DOIs	https://doi.org/10.1002/jcla.23100
Publication status	Published - Mar 2020

Keywords

cefuroxime
hypoalbuminemia
intensive care unit
therapeutic drug monitoring
unbound concentration
PROTEIN-BINDING

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van Raaij, J. J., Mabelis, N. J. D., Shudofsky, K. N., Meenks, S. D., le Noble, J. L. M. L., & Janssen, P. K. C. (2020). Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure. Journal of Clinical Laboratory Analysis, 34(3), Article 23100. https://doi.org/10.1002/jcla.23100

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title = "Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure",

abstract = "Background Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. Methods Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). Results Intra-assay and inter-assay precision was",

keywords = "cefuroxime, hypoalbuminemia, intensive care unit, therapeutic drug monitoring, unbound concentration, PROTEIN-BINDING",

author = "{van Raaij}, {Joost J.} and Mabelis, {Noortje J. D.} and Shudofsky, {Kimberly N.} and Meenks, {Sjoerd D.} and {le Noble}, {Jos L. M. L.} and Janssen, {Paddy K. C.}",

note = "Funding Information: The authors thank Hai Holthuysen and Loes Simons, laboratory analysts in the Hospital Pharmacy Department, for performing laboratory measurements. Publisher Copyright: {\textcopyright} 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.",

year = "2020",

month = mar,

doi = "10.1002/jcla.23100",

language = "English",

volume = "34",

journal = "Journal of Clinical Laboratory Analysis",

issn = "0887-8013",

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van Raaij, JJ, Mabelis, NJD, Shudofsky, KN, Meenks, SD, le Noble, JLML & Janssen, PKC 2020, 'Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure', Journal of Clinical Laboratory Analysis, vol. 34, no. 3, 23100. https://doi.org/10.1002/jcla.23100

Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure. / van Raaij, Joost J.; Mabelis, Noortje J. D.; Shudofsky, Kimberly N. et al.
In: Journal of Clinical Laboratory Analysis, Vol. 34, No. 3, 23100, 03.2020.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure

AU - van Raaij, Joost J.

AU - Mabelis, Noortje J. D.

AU - Shudofsky, Kimberly N.

AU - Meenks, Sjoerd D.

AU - le Noble, Jos L. M. L.

AU - Janssen, Paddy K. C.

N1 - Funding Information: The authors thank Hai Holthuysen and Loes Simons, laboratory analysts in the Hospital Pharmacy Department, for performing laboratory measurements. Publisher Copyright: © 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.

PY - 2020/3

Y1 - 2020/3

N2 - Background Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. Methods Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). Results Intra-assay and inter-assay precision was

AB - Background Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. Methods Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). Results Intra-assay and inter-assay precision was

KW - cefuroxime

KW - hypoalbuminemia

KW - intensive care unit

KW - therapeutic drug monitoring

KW - unbound concentration

KW - PROTEIN-BINDING

U2 - 10.1002/jcla.23100

DO - 10.1002/jcla.23100

M3 - Article

C2 - 31785116

SN - 0887-8013

VL - 34

JO - Journal of Clinical Laboratory Analysis

JF - Journal of Clinical Laboratory Analysis

IS - 3

M1 - 23100

ER -

van Raaij JJ, Mabelis NJD, Shudofsky KN, Meenks SD, le Noble JLML , Janssen PKC. Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure. Journal of Clinical Laboratory Analysis. 2020 Mar;34(3):23100. Epub 2019 Nov 30. doi: 10.1002/jcla.23100

Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure

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