Development and characterization of a non-enzymatic electrochemical biosensor for rapid determination of sorbent-based extracted trazodone and doxepin in complicated samples.

BACKGROUND: Given the importance of achieving optimal therapeutical concentration in patients treated with antidepressants, this study investigates a novel technique for the simultaneous determination of trazodone (TRZ) and doxepin (DOX) in human plasma and serum samples for the first time. RESULTS: To achieve simultaneous determination of two antidepressants, TRZ and DOX, a novel detection system was designed: a non-enzymatic voltammetric biosensor based on boron-reduced graphene oxide/manganese oxide nanoparticles (GCE/B-rGO/MnO NPs). The detection was accomplished after pre-concentration and extraction trace amounts of the analytes using the thin film-solid phase microextraction (TF-SPME) technique, which employed polyvinyl alcohol/polyvinyl acetate/copper oxide nanoparticles (PVA/PVAc/CuO NPs) electrospun nanofibers. The successful preparation of composite nanofibers and modified electrodes was confirmed using the evaluation of field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDX). Also, the composite nanofibers were characterized with attenuated total reflectance-Fourier transform-infrared (ATR-FT-IR) and X-ray diffraction (XRD). In the solution of TRZ and DOX, under optimum experimental conditions, the linear dynamic ranges (LDRs) were 0.1-20.0 µmol L-1 and 0.5-27.0 µmol L-1, respectively. Also, the limit of detection (LOD) values of TRZ and DOX were 0.032 and 0.150 µmol L-1. SIGNIFICANCE: PVAc acts as a cross-linking agent for PVA, and their mixture is effective for sample preparation and pre-concentration of analytes in complex matrices. Also, adding CuO NPs to this polymeric mixture enhanced the adsorption efficiency. Taking advantage of the high surface area of MnO NPs and the high electrical conductivity of B-rGO, and considering the superiority of their simultaneous utilization, the constructed electrochemical biosensor is both cost-effective and rapid. It demonstrates excellent stability, repeatability, and sensitivity for the simultaneous determination of TRZ and DOX under optimal conditions. This biosensor, the first of its kind, is specifically designed for the simultaneous determination of TRZ and DOX in human plasma and serum samples, representing a significant advancement in biosensing technology.

New Pharmaceutical Salts of Trazodone.

New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.

Comparative study on photocatalytic degradation of the antidepressant trazodone using (Co, Fe and Ru) doped titanate nanowires: Kinetics, transformation products and in silico toxicity assessment.

Titanate nanomaterials have been outstanding in the removal of emerging contaminants by the photocatalysis process. These photocatalysts, when modified through techniques such as doping with metals, they have advantages over TiO2, especially in the region of visible light. In this work, the photocatalytic performance of four recent reported catalysts, pristine titanate nanowires, cobalt-doped titanate nanowires, iron-doped titanate nanowires and ruthenium-doped titanate nanowires, for the removal of the antidepressant trazodone under visible light radiation was compared. The iron-doped titanate nanowires presented the best catalytic activity by the catalyst surface area. Additionally, thirteen transformation products (TPs) were identified by high-resolution mass spectrometry and, to the best of our knowledge, nine of them have never been described in the literature. It was shown that for each catalyst different TPs were formed with distinct time profiles. Finally, toxicity assessment by computational methods showed that TPs were not readily biodegradable and they presented toxicity to aquatic organisms with mutagenic potential. These findings reinforce the importance of taking into consideration the TPs formed during the removal of pollutants since many of them may be toxic and can be produced during photocatalysis.

Comparative study of ß-cyclodextrin, γ-cyclodextrin and 4-tert-butylcalix[8]arene ionophores as electroactive materials for the construction of new sensors for trazodone based on host-guest recognition.

BACKGROUND: Trazodone (TRZ) is a second-generation non-tricyclic antidepressant derived from a triazolopyridine derivative, which is mainly used to treat emotional disorders and conditions related to depressive disorders. PURPOSE: This study investigated the design, development and characteristics of polyvinyl chloride (PVC) membrane sensors for trazodone HCl (TRZ). METHODS: The developed sensing membranes were constructed using ß-cyclodextrin (ß-CD; sensor 1), γ-cyclodextrin (γ-CD; sensor 2) or 4-tert-butylcalix[8]arene (t-BC8; sensor 3) ionophores as sensing materials in addition to ionic sites and dioctyl phthalate in the PVC matrix. RESULTS: Sensors 1, 2 and 3 displayed fast, stable and near-Nernstian response over a relatively wide trazodone concentration range (7.0×10-6-1×10-3, 5.0×10-5-1×10-3and 8.0×10-6-1.0×10-3 M, respectively), with detection limits of 2.2×10-6, 1.5×10-5 and 2.42×10-6 M, respectively in the pH range of 3.0-6.0. The sensors demonstrated good selectivity for TRZ in the presence of different ionic compounds. The accuracy and precision of the proposed sensors were assessed by the determination of 40.7 µg/ml of TRZ, which showed average recoveries of 99.6%, 99.1% and 98.5% with mean relative standard deviations of 2.4%, 2.5% and 2.6% for sensor 1, 2 and 3 respectively. Molecular modeling was used to calculate the host-guest binding energy. The lowest free binding energy was -6.243, -5.752 and -5.7105 kcal/mol for 1:1 stoichiometry host-guest complexes of trazodone and ß-CD, γ-CD and t-BC8, respectively, which was in-line with a Nernstian response. CONCLUSION: The investigated methods can be applied for the determination of TRZ in pharmaceutical preparations. The results of investigated dosage-form of TRZ show good agreement with those using the US Pharmacopeia method.

Enhanced chemiluminescence for trazodone trace analysis based on acidic permanganate oxidation in concurrent presence of rhodamine 6G.

A new sensitized chemiluminescence method by acidic permanganate oxidation was developed for the sensitive determination of trazodone. A fluorescent dye as used rhodamine 6G to increase a chemiluminescence intensity. Under optimum conditions, the liner range of the calibration curve was obtained for 1-5000 nmol/L. The limit of detection was calculated from 3σ of a blank was 0.23 nmol/L. The coexistent ions and substances had no interference with the chemiluminescence measurement. The chemiluminescence spectra were measured to elucidate a possible mechanism for the system. The present method was satisfactorily used in the determination of the drugs in pharmaceutical samples and animal serums.

Spectroscopic and calorimetric studies on trazodone hydrochloride-phosphatidylcholine liposome interactions in the presence and absence of cholesterol.

The interaction of antidepressant drug trazodone hydrochloride (TRZ) with dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposomes (MLVs) in the presence and absence of cholesterol (CHO) was investigated as a function of temperature by using Electron Paramagnetic Resonance (EPR) spin labeling, Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC) techniques. These interactions were also examined for dimyristoyl phosphatidylcholine (DMPC) multilamellar liposomes by using Electron Paramagnetic Resonance (EPR) spin labeling technique. In the EPR spin labeling studies, 5- and 16-doxyl stearic acid (5-DS and 16-DS) spin labels were used to monitor the head group and alkyl chain region of phospholipids respectively. The results indicated that TRZ incorporation causes changes in the physical properties of PC liposomes by decreasing the main phase transition temperature, abolishing the pre-transition, broadening the phase transition profile, and disordering the system around the head group region. The interaction of TRZ with unilamellar (LUV) DPPC liposomes was also examined. The most pronounced effect of TRZ on DPPC LUVs was observed as the further decrease of main phase transition temperature in comparison with DPPC MLVs. The mentioned changes in lipid structure and dynamics caused by TRZ may modulate the biophysical activity of membrane associated receptors and in turn the pharmacological action of TRZ.

Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence detector coupled with strong cation exchange chromatographic column: application to a pharmacokinetic study in Chinese healthy volunteers.

A simple, selective, and sensitive high performance liquid chromatography (HPLC) procedure has been developed for determination of trazodone in human plasma. Prazosin was employed as the internal standard (IS). Sample preparation involved liquid-liquid extraction by methyl tert-butyl ether after alkalinization with ammonia. The HPLC separation was performed on a CAPCELL PAK SCX column (250mm×4.6mm, 5.0µm, Shiseido, Japan) with a mobile phase of acetonitrile/80mmol/L ammonium phosphate (pH adjusted to 6.0) (60:40, v/v) at a flow rate of 1.2mL/min. The peaks were detected by using fluorescence detector (excitation wavelength 320nm and emission wavelength 440nm). The extraction recovery was 72.6-88.3% and the method was over the concentration range of 5.0-2486ng/mL with a lower limit of quantitation (LLOQ) of 5.0ng/mL using 300µL of plasma. The intra- and inter-day accuracy of the method at three concentrations ranged from 96.7% to 104.2% for trazodone with precision of 2.9-3.7%. This validated method was successfully applied to a pharmacokinetic study enrolling 12 Chinese volunteers administered a single oral trazodone hydrochloride extended-release tablet of 75mg.

Effect of 70-nm silica particles on the toxicity of acetaminophen, tetracycline, trazodone, and 5-aminosalicylic acid in mice.

Exposure to nano-sized particles is increasing because they are used in a wide variety of industrial products, cosmetics, and pharmaceuticals. Some animal studies indicate that such nanomaterials may have some toxicity, but their synergistic actions on the adverse effects of drugs are not well understood. In this study, we investigated whether 70-nm silica particles (nSP70), which are widely used in cosmetics and drug delivery, affect the toxicity of a drug for inflammatory bowel disease (5-aminosalicylic acid), an antibiotic drug (tetracycline), an antidepressant drug (trazodone), and an antipyretic drug (acetaminophen) in mice. Co-administration of nSP70 with trazodone did not increase a biochemical marker of liver injury. In contrast, co-administration increased the hepatotoxicity of the other drugs. Co-administration of nSP70 and tetracycline was lethal. These findings indicate that evaluation of synergistic adverse effects is important for the application of nano-sized materials.

Evaluation of the interaction between ß-cyclodextrin and psychotropic drugs by surface plasmon resonance assay with a Biacore ® system.

Phase-solubility studies have been used to evaluate the solubilizing effects of cyclodextrins (CDs) on lipophilic, water-insoluble drugs. However, large amounts of CDs and drugs are required to measure solubility by phase-solubility studies. Thus, more efficient approaches to evaluate the interaction of CDs with drugs are needed. Herein we introduce a method that evaluates the interaction between immobilized ß-cyclodextrin and psychotropic drugs by surface plasmon resonance assay with a Biacore(®) system. Association constants and stoichiometries observed were generally consistent with values calculated by traditional methods, such as phase-solubility and continuous variation methods. Results showed that the analytical method using Biacore(®) was suitable to evaluate CD-drug interactions.

Ex vivo and in vivo evaluation of transdermal formulation of trazodone hydrochloride.

The aim of the present investigation is to evaluate the biopharmaceutical behaviors of the matrix patch containing trazodone hydrochloride (TZN) following transdermal administration in rabbits. The ex vivo skin permeation study was performed using Keshary-Chien glass diffusion cell and mouse epidermis with intact stratum corneum as membrane. The phosphate buffer of pH 7.4 was used as receptor solution at 37 degrees C. TZN patch was applied to the inner pinna skin of the rabbit. TZN transdermal absorption from patch was compared to that from peroral TZN solution in rabbit. A steady-state skin permeation rate of 134.09 +/- 2.49 microg/cm2/h was achieved from the matrix patch across mouse epidermis after an initial lag time of approximately 3.5 h. The steady-state transdermal TZN concentration of 2.3 microg/mL was achieved in rabbit from the matrix patch after an initial lag time of approximately 2 h. The Cmax of peroral TZN solution was calculated to be 5.84 microg/mL at a Tmax of 2 h indicating its rapid absorption compared to the transdermal administration with a Tmax of 5 h. The ex vivo and in vivo biopharmaceutical parameters were in good agreement with respect to steady-state plasma TZN concentration and lag time. The plasma level of TZN following transdermal application could be maintained for 24 h. The transdermal dose achieved a much higher steady-state blood concentration in rabbit compared with the effective blood concentration in human. The observed steady-state blood concentration may appear to be within the expected therapeutic range in human with a higher clearance value compared to that in rabbit.

Critical evaluation of buffering solutions for pKa determination by capillary electrophoresis.

The performance of the most common and also some other less common CE buffers has been tested for the pKa determination of several types of compounds (pyridine, amines, and phenols). The selected buffers cover a pH ranging from 3.7 to 11.8. Whereas some buffers, like acetic acid/acetate, BisTrisH+/BisTris, TrisH+/Tris, CHES/CHES-, and CAPS/CAPS- can be used with all type of analytes, others like ammonium/ammonia, butylammonium/butylammonia, ethylammonium/ethylammonia, diethylammonium/diethylammonia, and hydrogenphosphate/phosphate are not recommended because they interact with a wide range of compounds. The rest of the tested buffers (dihydrogenphosphate/hydrogenphosphate, MES/MES-, HEPES/HEPES-, and boric acid/borate) can show specific interactions depending on the nature of the analytes, and their use in some applications should be restricted.

HPLC analysis of the antidepressant trazodone and its main metabolite m-CPP in human plasma.

The present paper deals with the development of a rapid and feasible high-performance liquid chromatographic method for the determination of trazodone and its main active metabolite 3-(1-clorophenyl)piperazine (m-CPP) in human plasma. Trazodone is a second-generation antidepressant with serotonin antagonist activity. The metabolite seems to be involved in the onset of some side effects of trazodone therapy, thus its determination is very important during therapeutic drug monitoring. Separation was achieved using a C8 reversed-phase column and a mobile phase composed of aqueous phosphate buffer (70%), containing triethylamine, at pH 3.5 and acetonitrile (30%). The UV detector was set at 255 nm and loxapine was used as the internal standard. An original pre-treatment procedure of plasma samples was developed, based on solid-phase extraction with C8 reversed phase cartridges (50mg, 1 mL). The obtained extraction yields values were higher than 90% and precision, expressed as R.S.D., was lower than 5.6%. The method was successfully applied to plasma samples from depressed patients undergoing therapy with trazodone; accuracy results were satisfactory (recovery >91%). Thus, the method seems to be suitable for the therapeutic drug monitoring of trazodone and its main active metabolite in depressed patients' plasma.

Utility of 7,7,8,8-tetracyanoquinodimethane charge transfer reagent for the spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides.

A simple and rapid spectrophotometric method has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different pharmaceutical preparations. The charge transfer (CT) reaction between TZH, APH and ATPH as electron donors and TCNQ as electron acceptor was utilized for their spectrophotometric determination. The optimum experimental conditions, like time, temperature, stoichiometry, solvents, for the CT complex formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 10-400, 10-440 and 10-300 microg ml(-1), respectively. The sensitivity (S) is found to be 0.09, 0.087 and 0.069 g cm(-2) for TZH, APH and ATPH, respectively. The SD values are found to be 0.146-0.293, 0.154-0.285 and 0.091-0.212 and RSD values are 0.142-1.92, 0.297-1.92 and 0.212-0.915 for TZH, APH and ATPH, respectively. The low values of the relative standard deviation indicate the high accuracy and precision of the method. The mean recovery values obtained together with a high correlation coefficient values, amount in the range 98-101.5, 98.7-102.9 and 93-101.9 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Sensitive extractive spectrophotometric methods for the determination of trazodone hydrochloride in pharmaceutical formulations.

Two simple, rapid and sensitive extractive spectrophotometric methods have been developed for the assay of trazodone hydrochloride (TRH) in pure and pharmaceutical formulations. These methods are based on the formation of chloroform soluble ion-association complexes of TRH with bromothymol blue (BTB) and with bromocresol purple (BCP) in KCl-HCl buffer of pH 2.0 (for BTB) and in NaOAc-AcOH buffer of pH of 3.6 (for BCP) with absorption maximum at 423 nm and at 408 nm for BTB and BCP, respectively. Reaction conditions were optimized to obtain the maximum color intensity. The absorbance was found to increase linearly with increase in concentration of TRH, which was corroborated by the calculated correlation coefficient values (0.9996, 0.9945). The systems obeyed Beer's law in the range of 0.2-14.5 and 0.2-14.1 microg/ml for BTB and BCP, respectively. Various analytical parameters have been evaluated and the results have been validated by statistical data. No interference was observed from common excipients present in pharmaceutical formulations. The proposed methods are simple, accurate and suitable for quality control applications.

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation with molybdenum and thiocyanate.

Extraction spectrophotometric method has been developed for the determination of tricyclic drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in the dosage forms coming from different Egyptian markets. The method based on the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo(V)-thiocyanate followed by its extraction with methylene chloride. The optimum conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over the concentration range of 2-28, 2-32 and 1-30 microg ml(-1), respectively. The Sandell sensitivity (S) is found to be 0.105, 0.138 and 0.118 g cm(-2) for TZH, APH and ATPH, respectively. The SD is found to be 0.16-0.377, 0.12-0.259 and 0.091-0.286 and the R.S.D. are 0.14-0.55, 0.12-0.399 and 0.095-0.485 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation using methyl orange and bromocresol green reagents.

A simple and rapid extraction spectrophotometric procedure has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different dosage forms. The method involves the formation of intense yellow ion-pairs between these drugs under investigation and methyl orange (MO) and bromocresol green (BCG) reagents followed by their extraction with 1,2-dichloroethane and quantitative microdetermination at 420 and 410 nm using MO or BCG, respectively. The optimum experimental conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 2-50, 2-50 and 1-25 microg ml(-1) for TZH, APH and ATPH, using MO and 1-25 microg ml(-1) for TZH, APH and ATPH, using BCG, respectively. The Sandell sensitivity (S) is found to be 0.106, 0.1071 and 0.0907 g cm(-2) for TZH, APH and ATPH, respectively, using MO reagent and 0.0788, 0.0661 and 0.0494 g cm(-2) for TZH, APH and ATPH, respectively, using BCG. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Development of a liquid chromatography/electrospray tandem mass spectrometry assay for the quantification of apicidin, a novel histone deacetylase inhibitor, in rat serum: application to a pharmacokinetic study.

Apicidin, a fungal metabolite isolated from Fusarium pallidoroseum, is a cyclic tetrapeptide that exhibits potent anti-protozoal and anti-angiogenic activities. Although extensive studies have been recently conducted to examine the biological and pharmacological action, no information is available on the quantitative analysis of apicidin. To our knowledge, this study is the first to describe a rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method for the quantification of apicidin in rat serum. The method was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification (LLOQ), accuracy, and precision. The multiple reaction monitoring was based on the transitions m/z 624.7 --> 84.3 and 372.1 --> 176.1 for apicidin and trazodone, respectively. The assay utilized a single liquid-liquid extraction and isocratic elution, and the LLOQ was 0.5 ng/mL using 0.1 mL of rat serum. The assay was linear over a range from 0.5-1000 ng/mL, with correlation coefficients >0.9994. The mean intra- and inter-day assay accuracy ranged from 99.9-101.5% and 94.8-102.1%, respectively, and the mean intra- and inter-day precision was between 2.7-5.9% and 1.6-11.5%, respectively. The developed assay method was applied to a pharmacokinetic study after intravenous injection of apicidin in rats at a dose of 1 mg/kg.

An automated approach to salt selection for new unique trazodone salts.

PURPOSE: The purpose of this study was to establish an automated approach to salt selection and to search for unique trazodone salts for new applications. METHODS: Automated procedures were developed on a Biomek 2000 automation workstation with stacker and plate reader capabilities. Trazodone was dispensed into 96-well plates, and an automated method was set up to form 104 trazodone salts. Salts were observed under a polarized light microscope to determine crystallinity. After stepwise eliminations, the remaining salts were scaled-up and subjected to differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), hygroscopic, pH-solubility, density, surface area, and particle size analyses. RESULTS: Oils formed in several cases resulting in preliminary elimination of mesyl and esyl salts and four crystallizing solvents. Crystallinity was observed in 34 of 44 scaled-up trazodone salts. PXRD, DSC, and hygroscopic analyses indicated a number of new salts that were comparable in physicochemical parameters to the marketed HCl salt. Among them, the tosylate salt showed uniqueness for new applications. CONCLUSIONS: Automated procedures can be developed to increase the efficiency of pharmaceutical salt selection. The new tosylate salt gave a unique pH-solubility profile with low solubility over the entire pH range making it a potential candidate for a suspension or prolonged action formulation.

New colorimetric methods for the determination of trazodone HCl, famotidine, and diltiazem HCl in their pharmaceutical dosage forms.

Two sensitive and simple spectrophotometric methods are developed for the determination of trazodone HCl, famotidine, and diltiazem HCl in pure and pharmaceutical preparations. The methods are based on the oxidation of the cited drugs with iron(III) in acidic medium. The liberated iron(II) reacts with 1,10-phenanthroline (method A) and the ferroin complex is colorimetrically measured at 510 nm against reagent blank. Method B is based on the reaction of the liberated Fe(II) with 2,2-bipyridyl to form a stable colored complex with lambda(max )at 520 nm. Optimization of the experimental conditions was described. Beer's law was obeyed in the concentration range of 1-5, 2-12, and 12-32 microg mL(-1) for trazodone, famotidine, and diltiazem with method A, and 1-10 and 8-16 microg mL(-1) for trazodone and famotidine with method B. The apparent molar absorptivity for method A is 1.06x10(5), 2.9x10(4), 1.2x10(4) and for method B is 9.4x10(4 )and 1.6x10(4), respectively. The suggested procedures could be used for the determination of trazodone, famotidine, and diltiazem, both in pure and dosage forms without interference from common excipients.

Voltammetric analysis of trazodone HCl in pharmaceuticals and biological fluids.

The voltammetric behavior of trazodone (TRZ) HCl was studied using direct current (DC(t)), differential pulse (DPP) and alternating current (AC(t)) polarography. The drug manifests cathodic waves over the pH range of 10-14. The waves were characterized as being irreversible, diffusion-controlled with limited adsorption properties. At pH 10, the diffusion current-concentration relationship was found to be rectilinear over the range 4-32 and 0.8-24 microg ml(-1) using DC(t) and DPP modes, respectively, with minimum detectability (S/N=2) of 0.104 microg ml(-1) (2.45 x 10(-6) M) and 0.314 microg ml(-1) (7.397 x 10(-6) M) using the DPP and DC(t) modes, respectively. The diffusion-current constant (I(d)) is 4.31+/-0.02 (n=6). The proposed method was successfully applied to the determination of the studied compound either in pure form or in formulations. The results obtained were favorably compared with those given using a reference method. Furthermore, the proposed method was applied to the determination of TRZ in spiked human urine and plasma adopting the DPP technique. No prior extraction step is needed in case of urine. The percentage recoveries were 98.43+/-0.79 and 97.44+/-0.705 (n=4) in spiked human urine and plasma, respectively. A pathway for the electrode reaction was postulated.