A universal surrogate matrix assay for urea measurement in clinical pharmacokinetic studies of respiratory diseases.


Journal

Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241

Informations de publication

Date de publication:
Oct 2023
Historique:
revised: 07 07 2023
received: 19 06 2023
accepted: 19 07 2023
medline: 18 9 2023
pubmed: 7 8 2023
entrez: 6 8 2023
Statut: ppublish

Résumé

In pharmacokinetic studies for respiratory diseases, urea is a commonly used dilution marker for volume normalization of various biological matrices, owing to the fact that urea diffuses freely throughout the body and is minimally affected by disease states. In this study, we developed a convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) surrogate matrix assay for accurate urea quantitation in plasma, serum and epithelial lining fluid. Different mass spectrometer platforms and ionization modes were compared in parallel. The LC method and mass spectrometer parameters were comprehensively optimized to reduce interferences, to smooth the baseline and to maximize the signal-to-noise ratio. Saline was selected as the surrogate matrix, and its suitability was confirmed by good parallelism and accurate quality control sample measurements. Reliable and robust assay performance was demonstrated by precision and accuracy, dilution integrity, sensitivity, recovery and stability, all of which met bioanalysis requirements to support clinical studies. The assay performance was also verified and better understood by comparing it with a colorimetric assay and to a surrogate analyte assay. The newly developed surrogate matrix assay has the potential to be further expanded for urea quantitation in numerous physiological matrices.

Identifiants

pubmed: 37544926
doi: 10.1002/bmc.5713
doi:

Substances chimiques

Urea 8W8T17847W

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e5713

Informations de copyright

© 2023 John Wiley & Sons Ltd.

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Auteurs

Yang Tang (Y)

Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, California, USA.

Michael Van Parys (M)

Department of Bioanalytical Chemistry, LabCorp Early Drug Development, Madison, Wisconsin, USA.

Abigail Walker (A)

Department of Bioanalytical Chemistry, LabCorp Early Drug Development, Madison, Wisconsin, USA.

Alexandra Drelick (A)

Department of Bioanalytical Chemistry, LabCorp Early Drug Development, Madison, Wisconsin, USA.

Xiaorong Liang (X)

Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, California, USA.

Brian Dean (B)

Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, California, USA.

Liuxi Chen (L)

Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, California, USA.

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Classifications MeSH