This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ahsman, M. J.
Right arrow Articles by Mathot, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahsman, M. J.
Right arrow Articles by Mathot, R. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2009, p. 75-80, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00636-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates{triangledown}

Maurice J. Ahsman,1* Enno D. Wildschut,2 Dick Tibboel,2 and Ron A. Mathot1

Department of Hospital Pharmacy (Clinical Pharmacology Unit), Erasmus University Medical Center, 's-Gravendijkwal 230, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands,1 Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus University Medical Center, ’s-Gravendijkwal 230, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands2

Received 15 May 2008/ Returned for modification 18 September 2008/ Accepted 18 October 2008

Rational dosing of antibiotics in neonates should be based on pharmacokinetic (PK) parameters assessed in specific populations. PK studies of neonates are hampered by the limited total plasma volume, which restricts the sample volume and sampling frequency. Available drug assay methods require large sample volumes and are labor-intensive or time-consuming. The objective of this study was to develop a rapid ultra-performance liquid chromatographic method with tandem mass spectrometry detection for simultaneous quantification of amoxicillin, meropenem, cefazolin, cefotaxime, deacetylcefotaxime, ceftriaxone, and vancomycin in 50 µl of plasma. Cleanup consisted of protein precipitation with cold acetonitrile (1:4) and solvent evaporation before reversed-phase chromatographic separation and detection using electrospray ionization tandem mass spectrometry. Standard curves were prepared over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 100% ± 15% and 15%, respectively, with acceptable matrix effects. Coefficients of variation for matrix effects and recovery were <10% over six batches of plasma. Stability in plasma and aqueous stocks was generally sufficient, but stability of meropenem and ceftriaxone in extracts could limit autosampler capacity. The instrument run time was approximately 3.50 min per sample. Method applicability was demonstrated with plasma samples from an extracorporeal membrane oxygenation-treated neonate. Different β-lactam antibiotics can be added to this method with additional ion transitions. Using ultra-performance liquid chromatography mass spectrometry, this method allows simple and reliable quantification of multiple antibiotics in 50 µl of plasma for PK studies of neonates.

* Corresponding author. Mailing address: Department of Hospital Pharmacy (Clinical Pharmacology Unit), Erasmus University Medical Center, 's-Gravendijkwal 230, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Phone: 31 10 7033202. Fax: 31 10 7032400. E-mail: m.ahsman{at}erasmusmc.nl

{triangledown} Published ahead of print on 27 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 75-80, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00636-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»