Determination of mazindol in human oral fluid by high performance liquid chromatography-electrospray ionization mass spectrometry.

Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography-mass spectrometry (LC-MS). The LC system consisted of an LC-MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2-20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers.

Study on detection of drugs in slimming health foods using GC-MS/MS.

The determination of five drugs, fenfluramine (FEN), N-nitrosofenfluramine (NFE), sibutramine (SIB), mazindol (MAZ) and phenolphthalein (PHP), was studied in slimming health foods using GC-MS/MS. These drugs have been detected at high rates, especially in slimming health foods. Prolonged or excessive consumption of non-approved or unauthorized pharmaceuticals may cause serious adverse health consequences. In this study, samples were extracted with methanol and ultrasonication. Analyses were performed by GC-MS/MS, using established MS/MS parameters in the electron ionization (EI) mode and chemical ionization (CI) mode. In the EI mode, the recoveries of five drugs from several types of slimming health foods such as tablets, capsules and tea-bags spiked at 1 µg/mg (except PHP, spiked at 4 µg/mg) were in the range of 85.0-110.7% and 100 µg/mg (except PHP, spiked at 200 µg/mg) were 94.9-102.9%, respectively. In the CI mode, good recoveries of 80.3-102.2% (spiked at low concentration) and 92.8-103.2% (spiked at high concentration) were also obtained. We evaluated the present method using four slimming health foods, in which drugs had previously been detected. The results were similar to the previous results. These findings indicate that the present procedure for evaluating five drugs in slimming health foods by means of GC-MS/MS is useful.

[Determination of fenfluramine, diethylpropion and mazindol in slimming foods by gas chromatography-mass spectrometry].

A gas chromatography-mass spectrometry (GC/MS) analytical method for three anorectics drugs, fenfluramine, diethylpropion and mazindol, illegally adulterated in slimming foods has been developed. They can be simultaneously identified and quantified. The samples were extracted with chloroform, and then separated by GC with an HP-5MS GC capillary column. The temperature programming was started at 70 degrees C. The temperature was held at this temperature for 2 min and then increased at 10 degrees C/min to 280 degrees C. The completely separated peaks were identified by MS with a quadrupole mass filter and quantitated in selected ion monitoring mode. Compared with the NIST98 library, the matching qualities of the drugs in foods were all over 90%. The calibration curves of the drugs were excellent with correlation coefficients between 0.9991 and 0.9999, and relative standard deviations between 1.6% and 2.2%. The recoveries were between 96.0% and 102.4%. The results demonstrated that this method is suitable for the identification and quantitation of these anorectics drugs in slimming foods.

Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism.

Metabotropic glutamate receptors (mGluRs) have recently been considered as potential pharmacological targets in the treatment of neurodegenerative disorders and particularly in parkinsonism. Within the basal ganglia, receptors of group I (mGluR1 and mGluR5) are widely expressed; the present study was thus aimed at blocking these receptors in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease in the rat. Considering the prominent expression of mGluR5, we have used the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) to target these receptors. In rats trained to quickly depress a lever after a visual cue, bilateral lesions of the dopaminergic nerve terminals in the striatum produced severe akinetic deficits, which were expressed by increases in delayed responses and reaction times. Acute MPEP injection (1.5, 3, and 6 mg/kg, i.p.) had no effect, whereas chronic administration, ineffective in a control group, significantly reversed the akinetic deficits. Alleviation of these deficits was seen after 1 week of treatment, and the preoperative performance was fully recovered after a 3 week treatment of MPEP at all doses. Chronic MPEP also induced ipsilateral rotation in the unilateral 6-OHDA circling model. However, no effect was seen of MPEP (1.5, 3, or 6 mg/kg, i.p.) on haloperidol-induced catalepsy (1 mg/kg, i.p.). Altogether, these results suggest a specific role of mGluRs in the regulation of extrapyramidal motor functions and a potential therapeutic value for mGluR5 antagonists in the treatment of Parkinson's disease.

Solvolysis of a substituted imidazoline, mazindol.

Hydrolysis of mazindol to form 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine was followed spectro-photometrically in aqueous solutions at temperatures between 37 and 70degree, pH values up to 7.6, and an ionic strength of 0.2. The effects of acetate, formate, and phosphate buffers as well as ionic strength on the observed rate constants were investigated. An interesting nonlinear dependency of the kobs with buffer concentration was noted. The velocity constants declined with increasing hydrogen-ion concentration; the log k-pH profile and rate law are given along with other relevant data.

Structure determination of the anorexic agent mazindol.

The anorexic agent mazindol was shown to exist as the carbinolamine tautomer 5-p-chlorophenyl-2,3-dihydro-5H-imidazol[2,1-a]isoindol-5-ol in solution and in the solid state. The latter was established by diffuse UV reflectance spectroscopy.