Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose administration of clobenzorex.
Clobenzorex (Asenlix) is an anorectic drug used as part of a weight-management program. The drug is metabolized by the body to amphetamine, which is then excreted in the urine, thus causing difficulty in interpretation of amphetamine-positive drug tests. Previous studies have shown that the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h following administration of a single dose. However, the parent drug was not always detected in samples that contained amphetamine at > or =500 ng/mL, the administrative cutoff for a positive result. Consequently, the parent compound clobenzorex is not ideal for ascertaining whether the drug was the origin of the amphetamine. Several metabolites of clobenzorex have been shown to be detected for a longer period of time than the parent. One of these, a hydroxy metabolite, was shown to be detected for an extended period of time. In a study of urine samples provided following administration of a single 30-mg dose of this drug, 4-hydroxyclobenzorex could be detected for up to 91.5 h. More significantly, that study showed all samples that were positive for amphetamine also contained detectable amounts of 4-hydroxyclobenzorex. This metabolite proved to be easily detected and was typically found at higher levels than amphetamine in urine samples positive for amphetamine long after clobenzorex itself could no longer be detected. The present study analyzed samples from a controlled multidose administration (30 mg of clobenzorex daily for seven days) for the presence of 4-hydroxyclobenzorex. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and gas chromatographic-mass spectrometric analysis with monitoring of ions at m/z 125, 330, and 364 for 4-hydroxyclobenzorex and its 3-Cl regioisomer, which was used as an internal standard. Peak concentrations of 4-hydroxyclobenzorex ranged from 17,786 to 99,044 ng/mL. Most importantly, this study also found that all samples that contained amphetamine at > or =500 ng/mL also contained detectable amounts of this hydroxy metabolite (LOD 10 ng/mL), making it a valuable tool in differentiating use of clobenzorex from illicit amphetamine use.
Cody
J T
JT
AMEDD C & S, MCCS-HMP PA Branch, Fort Sam Houston, Texas 78234-6138, USA.
Valtier
S
S
D000661:Amphetamine / Q000652:urine*; D000662:Amphetamines / Q000493:pharmacokinetics / Q000652:urine*; D001067:Appetite Depressants / Q000493:pharmacokinetics*; D001711:Biotransformation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008297:Male
C420127:4-hydroxyclobenzorex; D000662:Amphetamines; D001067:Appetite Depressants; C000490:clobenzorex; D000661:Amphetamine