A quick approach for medetomidine enantiomer determination in dog plasma by chiral liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study

Bardhi, Anisa; Zaghini, Anna; Levionnois, Olivier; Barbarossa, Andrea (2021). A quick approach for medetomidine enantiomer determination in dog plasma by chiral liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study. Drug testing and analysis, 13(7), pp. 1249-1255. Wiley 10.1002/dta.3015

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In the present study, a rapid, sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of medetomidine enantiomers in dog plasma was developed and validated. The separation and individual quantification of chiral compounds can be a tricky task in LC. This is particularly true when target analytes have a relatively small mass, as is the case with medetomidine, a potent and highly specific α2-adrenoceptor agonist widely used in both human and veterinary medicine. The proposed approach is based on a quick liquid-liquid extraction with ethyl acetate and filtration prior to injection. The optimized mobile phase composition allowed to perfectly separate the two enantiomers of medetomidine in a short chromatographic run time, using a cellulose tris(4-methylbenzoate)-based chiral column. A lower limit of quantification of 0.1 ng/mL was reached for both analytes thanks to the high sensitivity and selectivity of MS/MS and the use of racemic medetomidine-d3 as internal standard prevented potential matrix effect. Linearity was satisfying (R2 > 0.99) over the range 0.1-25 ng/mL, as well as within- and between-session accuracy and precision, both always <15%. This method was also applied with success to a series of samples from a pharmacokinetic (PK) study aimed at comparing dex- and levomedetomidine behaviour after administration of the racemic mixture in dogs. The simple extraction procedure, which allows reduced solvent and time consumption without compromising analytical performances, makes this technique a useful tool for this kind of applications even when small animals are involved, due to the small amount of sample required.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Anaesthesiology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)

UniBE Contributor:

Levionnois, Olivier

Subjects:

600 Technology > 630 Agriculture

ISSN:

1942-7603

Publisher:

Wiley

Language:

English

Submitter:

Claudia Spadavecchia

Date Deposited:

16 Feb 2022 16:05

Last Modified:

17 Apr 2024 16:04

Publisher DOI:

10.1002/dta.3015

PubMed ID:

33569906

BORIS DOI:

10.48350/165011

URI:

https://boris.unibe.ch/id/eprint/165011

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