Determination of Thyreostats in Urine Using Supported Liquid Extraction and Mixed-Mode Cation-Exchange Solid-Phase Extraction: Screening and Confirmatory Methods

Overview

Journal J Chromatogr Sci

Publisher Oxford University Press

Specialty Chemistry

Date 2018 Jun 8

PMID 29878072

Authors

Adam Tolgyesi

Anupam Giri

Eniko Barta

Thomas J McDonald

Virender K Sharma

Affiliations

Soon will be listed here.

Abstract

The application of thyreostats in livestock has been banned in the European Union since 1981, but these drugs are currently in the focus due to the natural occurrence of thiouracil (TU). Studies have been published on TU contamination in urine samples of animal and human origins without any drug administration of it. This paper presents new analytical methods to analyze thyreostats to support the legislation on the recommended concentration (RC) levels of these drugs. Both screening and confirmatory methods are developed for analyzing thyreostats in porcine and bovine urines using a liquid chromatography-tandem mass spectrometry technique. The new methods include a chemical derivatization with 3-iodobenzyl bromide, followed by novel purification approaches using supported liquid extraction and mixed-mode cation-exchange solid-phase extraction (SPE) for screening and confirmatory purposes, respectively. The optimized derivatization in combination with the cation-exchange SPE gives high sensitivity and reducing matrix effect of the analysis. The methods are validated in accordance with the guidelines for the validation of screening methods and European Commission Decision 2002/657/EC. The confirmatory method is used in the national monitoring plan. The detected levels of TU in urine samples are below the currently applicable RC level (10 μg L-1).

References

Matuszewski B, Constanzer M, Chavez-Eng C . Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem. 2003; 75(13):3019-30. DOI: 10.1021/ac020361s. View

Pinel G, Bichon E, Pouponneau K, Maume D, Andre F, Le Bizec B . Multi-residue method for the determination of thyreostats in urine samples using liquid chromatography coupled to tandem mass spectrometry after derivatisation with 3-iodobenzylbromide. J Chromatogr A. 2005; 1085(2):247-52. DOI: 10.1016/j.chroma.2005.06.055. View

Pinel G, Mathieu S, Cesbron N, Maume D, De Brabander H, Andre F . Evidence that urinary excretion of thiouracil in adult bovine submitted to a cruciferous diet can give erroneous indications of the possible illegal use of thyrostats in meat production. Food Addit Contam. 2006; 23(10):974-80. DOI: 10.1080/02652030600806370. View

Vanden Bussche J, Noppe H, Verheyden K, Wille K, Pinel G, Le Bizec B . Analysis of thyreostats: a history of 35 years. Anal Chim Acta. 2009; 637(1-2):2-12. DOI: 10.1016/j.aca.2008.08.027. View

Lohmus M, Kallaste K, Le Bizec B . Determination of thyreostats in urine and thyroid gland by ultra high performance liquid chromatography tandem mass spectrometry. J Chromatogr A. 2009; 1216(46):8080-9. DOI: 10.1016/j.chroma.2009.04.005. View

Vanden Bussche J, Vanhaecke L, Deceuninck Y, Verheyden K, Wille K, Bekaert K . Development and validation of an ultra-high performance liquid chromatography tandem mass spectrometry method for quantifying thyreostats in urine without derivatisation. J Chromatogr A. 2010; 1217(26):4285-93. DOI: 10.1016/j.chroma.2010.04.030. View

Vanden Bussche J, Vanhaecke L, Deceuninck Y, Wille K, Bekaert K, Le Bizec B . Ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry detection of naturally occurring thiouracil in urine of untreated livestock, domesticated animals and humans. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011; 28(2):166-72. DOI: 10.1080/19440049.2010.544681. View

Bussche J, Kiebooms J, De Clercq N, Deceuninck Y, Le Bizec B, De Brabander H . Feed or food responsible for the presence of low-level thiouracil in urine of livestock and humans?. J Agric Food Chem. 2011; 59(10):5786-92. DOI: 10.1021/jf200556x. View

Wozniak B, Zuchowska I, Zmudzki J, Jedziniak P, Korycinska B, Sielska K . Liquid chromatography tandem mass spectrometry with ion trap and triple quadrupole analyzers for determination of thyreostatic drugs in urine and muscle tissue. Anal Chim Acta. 2011; 700(1-2):155-66. DOI: 10.1016/j.aca.2011.02.021. View

10.

Vanden Bussche J, Sterk S, De Brabander H, Blokland M, Deceuninck Y, Le Bizec B . Thyreostatic drugs, stability in bovine and porcine urine. Anal Bioanal Chem. 2012; 403(10):2973-82. DOI: 10.1007/s00216-012-5739-7. View

11.

Tolgyesi A, Sharma V, Fekete S, Fekete J, Simon A, Farkas S . Development of a rapid method for the determination and confirmation of nitroimidazoles in six matrices by fast liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2012; 64-65:40-8. DOI: 10.1016/j.jpba.2012.02.013. View

12.

Kiebooms J, Bussche J, Hemeryck L, Fievez V, Vanhaecke L . Intestinal microbiota contribute to the endogenous formation of thiouracil in livestock. J Agric Food Chem. 2012; 60(32):7769-76. DOI: 10.1021/jf3017145. View

13.

Lega F, Contiero L, Biancotto G, Angeletti R . Determination of thyreostats in muscle and thyroid tissues by QuEChERS extraction and ultra-performance liquid chromatography tandem mass spectrometry. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013; 30(6):949-57. DOI: 10.1080/19440049.2013.780212. View

14.

Tolgyesi A, Sharma V, Fekete J . Confirmatory analysis of stanozolol metabolites in bovine, pig and sheep urines using an optimized clean-up and liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2013; 88:45-52. DOI: 10.1016/j.jpba.2013.08.019. View

15.

Schmidt K . In-house validation and factorial effect analysis of a liquid chromatography-tandem mass spectrometry method for the determination of thyreostats in bovine blood plasma. Anal Bioanal Chem. 2013; 406(3):735-43. DOI: 10.1007/s00216-013-7517-6. View

16.

Kiebooms J, Wauters J, Bussche J, Vanhaecke L . Validation of a quantitative method using liquid chromatography coupled to multiple mass spectrometry for thiouracil in feedstuffs used in animal husbandry. Anal Bioanal Chem. 2014; 407(15):4373-84. DOI: 10.1007/s00216-014-8347-x. View

17.

Wauters J, Bussche J, Le Bizec B, Kiebooms J, Dervilly-Pinel G, Prevost S . Toward a new European threshold to discriminate illegally administered from naturally occurring thiouracil in livestock. J Agric Food Chem. 2015; 63(5):1339-46. DOI: 10.1021/jf504475f. View

18.

Gentili A, De Pratti V, Caretti F, Perez-Fernandez V, Tomai P, Curini R . Residue analysis of thyreostats in baby foods via matrix solid phase dispersion and liquid chromatography - dual-polarity electrospray - tandem mass spectrometry. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2016; 33(12):1793-1802. DOI: 10.1080/19440049.2016.1241899. View