Development and validation of general plasma screening method for performance enhancing drugs in racehorses utilizing liquid chromatography–high‐resolution mass spectrometry (LC–HRMS)

Author:

Lomnicka Izabela1,Dubey Saurabh2,Waller Pamela1,Vora Dharmikkumar1,Dirikolu Levent1

Affiliation:

1. Equine Medication Surveillance Laboratory (EMSL), Department of Comparative Biomedical Sciences, School of Veterinary Medicine Louisiana State University Baton Rouge Louisiana USA

2. Biomarkers Core Laboratory, Irving Institute for Clinical and Translational Research Columbia University Medical Center New York New York USA

Abstract

AbstractThe screening of drugs in plasma and urine often requires initial extraction (such as liquid–liquid extraction and solid‐phase extraction) before the samples are submitted to instrumental analyses. These extraction procedures are often laborious and time‐consuming. In this manuscript, a high‐throughput automated assay based on liquid chromatography–high‐resolution mass spectrometry (LC–HRMS) suitable for use as an initial testing procedure covering multiple classes of compounds prohibited in horse racing is described. The assay requires a 600‐μL plasma aliquot, which is subjected to solid phase extraction (SPE) using OASIS HLB 96‐well SPE with Biotage Extrahera system, evaporation, and reconstitution in a 96‐well collection plate. LC–HRMS analyses were carried out on a Thermo Q‐Exactive Mass spectrometer coupled with Thermo UHPLC system equipped with Thermo Accela ALS 2.4.0 autosampler linked to ACE Excel column. Drug targets were detected by retention time and accurate mass, with a mass tolerance window of 5 ppm in positive and negative ionization mode. The screening method was validated for over 300 drug targets in a 13‐min run. Validation data including sensitivity, specificity, extraction recovery, and precision are presented. As the method employs full‐scan mass spectrometry, unlimited number of drug targets can theoretically be incorporated into this method.

Publisher

Wiley

Reference22 articles.

1. Efficient Use of Retention Time for the Analysis of 302 Drugs in Equine Plasma by Liquid Chromatography-MS/MS with Scheduled Multiple Reaction Monitoring and Instant Library Searching for Doping Control

2. Association of Racing Commission International (ARCI) Uniform Classification Guidelines for Foreign Substances and Recommended Penalties Model Rule. December 2020 (V.14.4). Accessed March 2023. (https://www.arci.com/wp-content/uploads/2020/12/Uniform-Classification-Guidelines-Version-14.4.pdf).

3. ARCI Endogenous Dietary or Environmental Substances Schedule‐Version 4.1. Accessed March 2023. (https://www.arci.com/wp-content/uploads/2019/12/ARCI_EDE_Schedule-V4_1-2019-12.pdf).

4. ARCI Controlled Therapeutic Medication Schedule for Horses ‐ Version 4.2.1. Accessed March 2023. (https://www.arci.com/model-rules-standards/).

5. H.R.1754. Horseracing Integrity and Safety Act of 2020. (https://www.congress.gov/bill/116th-congress/house-bill/1754/text).

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