Identification of trimetazidine metabolites in human urine and plasma

Abstract

1. The objective was to use modern mass spectrometric techniques to update current information on the metabolism of trimetazidine in human subjects found by previous studies. 2. Urine and plasma samples were taken from four healthy human volunteers taking part in a larger kinetic study. Each subject received an oral dose of 80-mg trimetazidine daily for 4 days. 3. Identification and quantitation of trimetazidine and its metabolites in urine and plasma were achieved using modern liquid chromatography-mass spectrometric methods. 4. The major drug-related component observed in urine and plasma was unchanged trimetazidine. In addition to the parent drug, 10 metabolites were detected in urine in concentrations ranging from 0.008 (0.01% dose) to 1.094 micrograms.ml-1 (1.4% dose). Metabolic profiles following acute and chronic doses of trimetazidine were qualitatively similar.

Evidence for the existence of [3H]‐trimetazidine binding sites involved in the regulation of the mitochondrial permeability transition pore

“…Indeed, [ 3 H]‐trimetazidine binding was observed in the microsomal fraction although it was devoid of cytochrome C oxidase activity and, thus, of mitochondria. These microsomal sites correspond probably to sites of biotransformations as trimetazidine is metabolized in man and in rats, probably in the liver (Harpey et al , 1989; Jackson et al , 1996). The large binding recovery in the nuclear fraction can be attributed to the presence of mitochondria, as assessed by cytochrome C oxidase activity remaining in this fraction.…”

Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure

“…Taking into account that trimetazidine is mainly excreted unchanged in urine [2] and that the target population is mostly elderly, possible changes in the pharmacokinetic profile as a result of increasing age and deteriorating renal function were investigated. The two studies were carried out in accordance with the recommendations of the Declaration of Helsinki [3] with applicable regulation on Good Clinical Practice (ICH E6-Guideline for good clinical practice-1996).…”

Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP)

“…The position of the oxo group could be assigned to position 2, because of the distinctive fragment ion at m / z 193, whereas the fragment ion at m / z 179 of N , N ‐bis‐dealkyl‐oxo‐MeOP (9) arose from an oxo group attached in position 3. Oxidation of a methylene group on the piperazine ring to the corresponding keto‐piperazine has been described, for example, the sedative‐hypnotic drug zopiclone, the antihistamine cyproheptadine, and trimetazidine …”