Journal of Chromatography B, 726 (1999) 141–148 Excretion study of the b -agonist reproterol in human urine 2 * C.G. Georgakopoulos , C. Tsitsimpikou, M.-H.E. Spyridaki Doping Control Laboratory of Athens, Olympic Athletic Center of Athens, Kifissias 37, 15123 Maroussi, Greece Received 13 August 1998; received in revised form 29 December 1998; accepted 8 January 1999 Abstract An excretion study of the b -agonist 7-[3-[( b-3,5-trihydroxyphenethyl)amino]-propyl]theophylline (reproterol) in human 2 urine, which is reportedly misused by athletes and horses as a doping agent, is presented. The study was performed after an oral administration of 20 mg of reproterol hydrochloride. The collected urine samples were prepared using the standard anabolic steroid extraction procedure and analyzed by gas chromatography coupled with quadrupole mass spectrometry and, also, with high-resolution mass spectrometry (HRMS). The main reproterol metabolite was found, whereas unchanged reproterol was not detected. The structure of the main metabolite was confirmed by an accurate HRMS measurement of diagnostic ions. Finally, an excretion urine profile of the main metabolite is presented. The mass spectrum of another possible unidentified reproterol metabolite is also reported.  1999 Elsevier Science B.V. All rights reserved. Keywords: Reproterol 1. Introduction inhalation, after prescription by a physician and declaration to the relevant medical authority prior to b -Agonists are a group of drugs designed for the competition [3]. 2 treatment of pulmonary diseases. However, adminis- The detection of b -agonists in biological fluids is 2 tration of such agents at high doses produces side a difficult analytical problem due to the low de- effects on protein synthesis and lipolysis resulting in tection limits at ng / ml levels. Many different meth- an anabolic effect [1]. The results from the doping ods have been described for their determination, but controls conducted during sport events or in out of the approach of choice is gas or liquid chromatog- competition tests, revealed an increasing use by the raphy with mass spectrometry (MS) [1,4–7]. athletes of the b -adrenoceptor agonists for apparent Reproterol (7-[3-h( b-3,5-trihydroxyphenethyl)- 2 therapeutic treatment [2]. Therefore, the International aminoj-propyl]theophylline), Fig. 1 (I), is a b -agon- 2 Olympic Committee (IOC) has introduced several ist with a similar to salbutamol effectiveness in b -agonists in the list of prohibited classes of controlling exercised-induced asthma [8], introduced 2 substances. Of the b -agonists, only salbutamol, this year in the list of IOC. Its molecule combines 2 salmeterol and terbutaline are allowed and only by the structure of a b -agonist with a xanthine group. 2 Its action as a xanthine has not yet been confirmed and only traces of theophylline have been detected in *Corresponding author. Tel.: 130-1-686-8549; fax: 130-1-686- blood of subjects after administration [9]. Biotrans- 8549. E-mail address: oaka@compulink.gr (C.G. Georgakopoulos) formation of reproterol in animals and in man leads 0378-4347 / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S0378-4347(99)00033-X