Analysis of serum tranexamic acid in patients undergoing open heart surgery.


Journal

Clinical biochemistry
ISSN: 1873-2933
Titre abrégé: Clin Biochem
Pays: United States
ID NLM: 0133660

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 31 05 2020
revised: 07 10 2020
accepted: 21 10 2020
pubmed: 15 11 2020
medline: 25 5 2021
entrez: 14 11 2020
Statut: ppublish

Résumé

Tranexamic acid is a drug used during open cardiac surgery to prevent blood loss. The blood levels of 10-100 µg/mL are reported to be in the therapeutic range and higher levels are linked to increased incidence of adverse effects. The aim of this study was to optimize and validate an LC-MS/MS method for serum tranexamic acid and measure its levels in patients from the DEPOSITION Pilot trial in order to prove the concept that topical administration will yield lower serum concentration. The method development was carried out in several steps including sample preparation, and optimization of chromatography and tandem mass spectrometry parameters. Method validation including day-to-day precision with 4 QC levels, limit of detection, sample stability, carryover, and concentration-signal linearity was carried out. Ninety patient samples were analyzed using the validated method. Fast and efficient LC-MS/MS method for analysis of tranexamic acid in serum was developed. The run time was 7 min with the total time of one hour including the sample preparation. The method precision was acceptable (%CV = 10.5-12.6%) with no sample carryover observed. The matrix effect on the analytical sensitivity was negligible and the lower limit of detection was 0.5 µg/mL. The difference in the mean adjusted concentrations between topical (45 patients) and intravenous (45 patients) groups was statistically significant (0.1154 µg/mL/kg vs. 0.2542 µg/mL/kg, p < 0.0001) CONCLUSIONS: Rapid and simple LC-MS/MS method for analysis of tranexamic acid was optimized and validated. The laboratory has played a crucial role in proving the concept that topical administration yields significantly lower systemic levels of tranexamic acid, and thus decreases the risk of adverse outcomes in patients undergoing open cardiac surgery.

Sections du résumé

BACKGROUND BACKGROUND
Tranexamic acid is a drug used during open cardiac surgery to prevent blood loss. The blood levels of 10-100 µg/mL are reported to be in the therapeutic range and higher levels are linked to increased incidence of adverse effects. The aim of this study was to optimize and validate an LC-MS/MS method for serum tranexamic acid and measure its levels in patients from the DEPOSITION Pilot trial in order to prove the concept that topical administration will yield lower serum concentration.
METHODS METHODS
The method development was carried out in several steps including sample preparation, and optimization of chromatography and tandem mass spectrometry parameters. Method validation including day-to-day precision with 4 QC levels, limit of detection, sample stability, carryover, and concentration-signal linearity was carried out. Ninety patient samples were analyzed using the validated method.
RESULTS RESULTS
Fast and efficient LC-MS/MS method for analysis of tranexamic acid in serum was developed. The run time was 7 min with the total time of one hour including the sample preparation. The method precision was acceptable (%CV = 10.5-12.6%) with no sample carryover observed. The matrix effect on the analytical sensitivity was negligible and the lower limit of detection was 0.5 µg/mL. The difference in the mean adjusted concentrations between topical (45 patients) and intravenous (45 patients) groups was statistically significant (0.1154 µg/mL/kg vs. 0.2542 µg/mL/kg, p < 0.0001) CONCLUSIONS: Rapid and simple LC-MS/MS method for analysis of tranexamic acid was optimized and validated. The laboratory has played a crucial role in proving the concept that topical administration yields significantly lower systemic levels of tranexamic acid, and thus decreases the risk of adverse outcomes in patients undergoing open cardiac surgery.

Identifiants

pubmed: 33188769
pii: S0009-9120(20)30872-9
doi: 10.1016/j.clinbiochem.2020.10.010
pii:
doi:

Substances chimiques

Tranexamic Acid 6T84R30KC1

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

74-78

Informations de copyright

Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Auteurs

Josko Ivica (J)

Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada. Electronic address: josko.ivica@medportal.ca.

Jeannette Gauthier (J)

Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada.

Patricia Power (P)

Hamilton Health Sciences, Hamilton, Ontario, Canada.

André Lamy (A)

Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.

Murray Potter (M)

Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada; Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada.

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Classifications MeSH