Analytica Chimica Acta 529 (2005) 361–369 Quantitative determination of dexamethasone in bovine plasma and tissues by liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry to monitor residue depletion kinetics Marc Cherlet ∗ , Siegrid De Baere, Siska Croubels, Patrick De Backer Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium Received 13 May 2004; received in revised form 7 July 2004; accepted 7 July 2004 Available online 17 August 2004 Abstract Dexamethasone (DXM) is a synthetic glucocorticoid that is authorized for therapeutic use in veterinary medicine. The European Community (EC) fixed a maximum residue limit (MRL) at 2 ng g -1 for liver, 0.75 ng g -1 for muscle and kidney tissues and 0.3 ng ml -1 for milk, while its use as a growth-promotor is completely banned. We developed earlier a LC–APCI–MS/MS method capable of quantifying such low MRL levels in milk. Minor modifications—concerning only the extraction procedure—were sufficient to allow the quantification of these levels as well in tissue samples. Validation results according to EC requirements concerning linearity, accuracy and precision were satisfactory. Limits of quantification of 0.375 ng g -1 were obtained for muscle and kidney tissues and of 1 ng g -1 for liver tissue, i.e. half the MRLs. Limits of detection were 0.09, 0.13 and 0.33 ng g -1 for muscle, kidney and liver tissues, respectively. Decision limits (CC) were 1.2 ng g -1 for muscle and kidney tissues and 2.2 ng g -1 for liver tissue, while detection capabilities (CC) were 1.8, 1.9 and 2.5 ng g -1 for muscle, kidney and liver tissues, respectively. A simple deproteinization step with concentrated trichloroacetic acid followed by an extraction with ethyl acetate was sufficient to quantify DXM in plasma samples with a limit of quantification of 1 ng ml -1 . After intravenous injection of DXM to cattle, a distribution within 30 min was observed followed by a phase of slow elimination characterized by a half-life of 9.2 h. In muscle tissue, low levels of DXM were found and a quick elimination was observed, with the DXM level falling below the MRL within 4 days after administration. Higher DXM levels were found in liver tissue compared to kidney tissue up to 4 days after administration. Nevertheless, in liver tissue DXM was below the MRL after 8 days of withdrawal time, while it was still as high as 2.5 ng g -1 in kidney tissue. © 2004 Elsevier B.V. All rights reserved. Keywords: Dexamethasone; LC–APCI–MS/MS; Quantification; Validation; Intravenous administration; Residue depletion kinetics 1. Introduction Dexamethasone (DXM) (9-fluoro-11,17,21-trihy- sdroxy-16-methylpregna-1,4-diene-3,20-dione) is a syn- thetic glucocorticoid derived from hydroxycortisone that has found widespread application in human as well as in vet- erinary medicine. In the latter, it is used in the treatment ∗ Corresponding author. Tel.: +32 9 264 73 24; fax: +32 9 264 74 97. E-mail address: mcherlet@yahoo.com (M. Cherlet). of metabolic diseases in ruminants, e.g. ketosis, and of in- flammatory diseases in a variety of animal species [1]. It is available as the free alcohol or in the form of differ- ent esters (phosphate, isonicotinate, phenylpropionate and dimethylbutyrate), and is usually administered either intra- muscularly or intravenously at doses ranging from 20 to 60 g of DXM kg -1 BW (body weight) [1]. Glucocorticoids are also illicitly used for their growth-promoting effect [2]. To protect consumer’s health, the latter use has been banned by the European Commission (EC) [3], while maximum residue 0003-2670/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2004.07.014