Investigative implications of the instability and metabolism of mebeverine

Abstract

The anti-spasmodic drug mebeverine is used in the treatment of irritable bowel syndrome. It has been found to be unstable and rapidly metabolized to initially form mebeverine-alcohol and veratric acid. Mebeverine-alcohol is a precursor for a number of amphetamine-like compounds. Consequently, these, in addition to mebeverine and mebeverine-alcohol, can produce false-positive amphetamine immunoassay results. Mebeverine is highly unstable in esterase-containing biological fluid (in particular blood and plasma), but it is largely stable in aqueous solutions and urine. Sodium fluoride did not appear to reduce mebeverine breakdown. Because of its unstable nature, mebeverine analysis should be performed as soon as possible after specimen receipt. Mebeverine, mebeverine-alcohol, and veratric acid concentrations should be measured in the blood/serum to assist interpretation; however, because of rapid metabolism/instability, mebeverine itself is rarely detected. In one fatal case of suspected mebeverine overdosage, mebeverine (1.2 mg/L), mebeverine-alcohol (74 mg/L), and veratric acid (127 mg/L) concentrations were measured in the postmortem blood; a high concentration of citalopram was also detected. In two fatalities involving possible therapeutic use, no mebeverine was detected, but mebeverine-alcohol (6.9 and 5.4 mg/L) and veratric acid (13.7 and 41.8 mg/L) were found by gas chromatography-mass spectrometry and high-performance liquid chromatography-diode-array detection (HPLC-DAD) and measured by HPLC-DAD. Only one case involving mebeverine has previously been published; this paper provides additional data and suggestions of best practice for case investigation.