Surfactant-assisted electromembrane extraction combined with cyclodextrin-modified capillary electrophoresis for the separation and quantification of Tranylcypromine enantiomers in biological samples.

Surfactant-assisted electromembrane extraction coupled with cyclodextrin-modified capillary electrophoresis was developed for the separation and determination of Tranylcypromine enantiomers in biological samples. This combination would provide a new strategy for selective and sensitive determination of target analytes. The addition of surfactant in the donor solution improved the analyte transport into the lumen of hollow fiber that resulted in an enhancement in the analytes migration into acceptor solution. Optimization of the variables, affecting proposed method, was carried out and best results were achieved with a 175 V potential as driving force of the electromembrane extraction, 2-nitrophenyloctylether as the supported liquid membrane, donor solution containing 0.2 mM Triton X-100 with pH 3 and 0.1 M HCl for acceptor solution. Then, the extract was analyzed using cyclodextrin-modified capillary electrophoresis method for separation of Tranylcypromine enantiomers. The best results were obtained with a phosphate running buffer (100 mM, pH 2.0) containing 7% w/v hydroxypropyl-α-cyclodextrin. Under the optimum conditions, a low limit of detection (3.03 ng/mL), good linearity (R2  > 0.9953), and relative standard deviations below 4.0% (n = 5) were obtained. Finally, this procedure was applied to determine the concentration of Tranylcypromine enantiomers in urine samples with satisfactory results.

Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality.

Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

Gas chromatography-mass spectrometry detection of a norfluoxetine artifact in hydrolyzed urine samples may falsely indicate tranylcypromine ingestion.

In several cases, fluoxetine, its metabolites, its known artifacts, and supposedly tranylcypromine were detected in urine using the authors' systematic toxicological analysis (STA) procedure based on acid hydrolysis, extraction, and acetylation. As fluoxetine and tranylcypromine are absolutely contraindicated drugs and in none of the cases was tranylcypromine prescribed, the question of whether the detected compound might have been formed by fluoxetine and/or its metabolites arose. Therefore, rat urine taken after dosing with fluoxetine was screened in the same way. In addition, aqueous solutions of fluoxetine, norfluoxetine, tranylcypromine, and a mixture of the latter two drugs were worked-up and analyzed according to the STA and without hydrolysis. In urine specimens obtained from rats dosed with fluoxetine, tranylcypromine was detected as well as in the solution of worked-up norfluoxetine including hydrolysis. Its underlying mass spectrum could be identified by detailed interpretation of the fragmentation patterns as acetylated 3-phenyl-propyl-2-ene-amine. This compound could be postulated as hydrolysis product of norfluoxetine formed by ether cleavage and water elimination. Although this spectrum shows nearly the same fragmentation patterns as that of acetylated tranylcypromine, both compounds could finally be differentiated by their retention indices and by using the positive-ion chemical ionization mode.

Direct separation of tranylcypromine enantiomers and their profile in an atypical depressive patient.

An isocratic and simple high-performance liquid chromatographic method is developed for the direct resolution of the tranylcypromine (TCP) enantiomers. The method involves the use of an S-18-crown-6-ether chiral stationary phase known as the Crownpak CR (+) column. The stereochemical separation factor (alpha) obtained was 1.30 and the stereochemical resolution factor (Rs) was 0.69 when using a mobile phase consisting of 0.1 N perchloric acid containing 12% methanol at 23 degrees C. The method has been used to monitor and identify, qualitatively, the profile of enantiomers of TCP in urine of an atypical depressive patient. It was found that the (-)-S-TCP concentration is significantly higher than the (+)-R-enantiomer.

The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers.

The pharmacokinetics of the two enantiomers of tranylcypromine were evaluated in six healthy subjects after oral dosage of the racemate (20 mg of the sulphate) and the single enantiomers (10 mg of the sulphate) using an enantiospecific assay. Significant differences in AUC, Cmax, lambda(z), and CLR of the two enantiomers were observed both on administration of the racemate and of the individual enantiomers. The plasma concentrations and urinary excretion rates of (-)-tranylcypromine exceeded those of (+)-tranylcypromine. AUCs of the (-)-enantiomer [arithmetical means 197 ng ml(-1) h after the racemate, 130 ng ml(-1) h after the enantiomer] were greater than those of the (+)-enantiomer [26 ng ml(-1) h after the racemate, 28 ng ml(-1) h after the enantiomer] (P = 0.0001). No in vivo racemisation was detected. The power of the study was insufficient to establish any enantiomer-enantiomer interaction except for a possible interaction at the level of renal clearance (P = 0.013 for both enantiomers).

Enantiospecific high-performance liquid chromatographic assay with fluorescence detection for the monoamine oxidase inhibitor tranylcypromine and its applicability in pharmacokinetic studies.

In order to be able to measure low concentrations of tranylcypromine enantiomers in biological material, chiral fluorescent derivatization and high-performance liquid chromatography (HPLC) were employed. The internal standard S-(+)-amphetamine and borate-sodium hydroxide buffer pH 11 were added to plasma or urine sample aliquots. o-Phthaldialdehyde was used for precolumn derivatization in combination with the chiral mercaptan N-acetylcysteine. HPLC resolution of the diastereoisomeric derivatives was possible on an octadecylsilane column. The mobile phase consisted of sodium phosphate buffer solution pH 6.5, methanol and tetrahydrofuran. The fluorescence of the eluate was monitored at 344/442 nm. The intra-day coefficients of variation were below 10%, the limit of determination was 0.5 ng/ml. The assay was found to be applicable for routine analyses in a preliminary pharmacokinetic study, in which an oral dose of 20 mg racemic tranylcypromine sulfate was administered to three healthy volunteers. The plasma concentrations were generally low, and those of S-(-)-tranylcypromine significantly exceeded those of the R-(+)-enantiomer. Average maximum concentrations were 57.5 and 6.3 ng/ml for S- and R-tranylcypromine, respectively. While S-tranylcypromine was well detectable within the whole study period (8 h), R-tranylcypromine concentrations fell below the detection limit after 4 h in two out of the three studied volunteers.

Detection and quantitation of a ring-hydroxylated metabolite of the antidepressant drug tranylcypromine.

The formation of p-hydroxytranylcypromine from intraperitoneally injected tranylcypromine was confirmed using two types of experiments. In the first, tranylcypromine levels were shown to be increased in brains of rats pretreated with agents known to be inhibitors of ring hydroxylation compared to rats pretreated with physiological saline. For the second set of experiments, p-hydroxytranylcypromine was identified in brain and urine (following intraperitoneal injection) by derivatizing with perfluoroacylating reagents and analyzing by electron-capture gas chromatography and by combined gas chromatography-mass spectrometry. In experiments in vitro, p-hydroxytranylcypromine was demonstrated to inhibit monoamine oxidase, although it was weaker than TCP in this regard and was a much stronger inhibitor of MAO-A than of MAO-B.

Determination of tranylcypromine in human plasma and urine using high-resolution gas--liquid chromatography with nitrogen-sensitive detection.

A precise and sensitive method is described for the determination of the antidepressant drug tranylcypromine in human plasma and urine using high-resolution gas chromatography. The drug, together with an added internal standard, is extracted from the plasma or urine sample, derivatized with heptafluorobutyric anhydride and analysed on an OV-225 support-coated open-tubular glass capillary column with nitrogen-sensitive detection. The method has been applied to the measurement of tranylcypromine levels in plasma and urine from both healthy volunteers and from psychiatric patients receiving a therapeutic dosage of the drug.

[Determination and comparison of the plasma and urine concentrations in men given tranylcypromine stereoisomers]. / Bestimmung und Vergleich der Plasma- und Urinkonzentrationen nach Gabe von (+)- und (-)-Tranylcypromin.

The (+) and (-)isomers of DL-trans-2-phenylcyclopropylamine (tranylcypromine, Parnate, Jatrosom) were tested under cross-over conditions on 10 volunteers. (-)Tranylcypromine entered blood circulation more rapidly, reached significantly higher concentrations and was metabolized more slowly than (+)tranylcypromine. These results indicate a difference in the pharmacokinetics of the tranylcypromine isomers. In the urine collected over a period of 24 h the excretion of unmetabolized (4)tranylcypromine was lower probably resulting from the greater metabolization rate of this isomer. There is a conformity between the findings in plasma and urine.