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LC-MS/MS quantification of free and Fab-bound colchicine in plasma, urine and organs following colchicine administration and colchicine-specific Fab fragments treatment in Göttingen minipigs.
- Source :
-
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2017 Aug 15; Vol. 1060, pp. 400-406. Date of Electronic Publication: 2017 Jun 20. - Publication Year :
- 2017
-
Abstract
- Clinical evaluation of a colchicine specific antigen-binding fragment (Fab) in order to treat colchicine poisoning required the development of an accurate method allowing quantification of free and Fab-bound colchicine in plasma and urine, and free colchicine in tissues, to measure colchicine redistribution after Fab administration. Three methods have been developed for this purpose, and validated in plasma, urine and liver: total colchicine was determined after denaturation of Fab by dilution in water and heating; free colchicine was separated from Fab-bound colchicine by filtration with 30KDa micro-filters; tissues were homogenized in a tissue mixer. Deuterated colchicine was used as internal standard. Samples were extracted by liquid-liquid extraction and analyzed with a LC-MS/MS. LOQ were 0.5ng/mL in plasma and urine for free and total colchicine and 5pg/mg in tissues. The methods were linear in the 0.5-100ng/mL range in plasma and urine, and 5-300pg/mg in tissues with determination coefficients>0.99. Precision and accuracy of QC samples presented a CV<9.4%. The methods require only 200μL of sample and allow a high throughput due to short analytical run (2min). These methods were successfully applied to a pig intoxicated with colchicine and treated with colchicine specific Fab fragments.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Colchicine administration & dosage
Colchicine chemistry
Colchicine metabolism
Immunoglobulin Fab Fragments chemistry
Immunoglobulin Fab Fragments metabolism
Limit of Detection
Linear Models
Reproducibility of Results
Swine
Swine, Miniature
Tissue Distribution
Chromatography, Liquid methods
Colchicine analysis
Immunoglobulin Fab Fragments analysis
Tandem Mass Spectrometry methods
Subjects
Details
- Language :
- English
- ISSN :
- 1873-376X
- Volume :
- 1060
- Database :
- MEDLINE
- Journal :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28667924
- Full Text :
- https://doi.org/10.1016/j.jchromb.2017.06.034