A novel electrochemical sensor based on electrode modified with gold nanoparticles and molecularly imprinted polymer for rapid determination of trazosin.

A novel molecularly imprinted polymer sensor for fast and direct determination of trazosine (TR) was studied. The voltammetric sensor based on molecularly imprinted polymer (MIP) with disposable gold nanoparticles modified screen printed carbon electrode (MIP/AuNPs/SPCE) is developed for the determination of TR. Under the optimum conditions, the peak current of the sensor and TR concentration showed a good linear relationship over the range from 2.0 to 250.0 µM, with a low detection limit (S/N = 3) of 0.3 µM. The modified electrode demonstrated good electrocatalytic properties toward the oxidation of TR. This sensor selectively detected TR even in the presence of high concentration of similar compounds and MIP/AuNPs/SPCE was also confirmed successfully for the determination of TR in the various real samples including human blood serum, urine and trazosin tablet.

Rayleigh light scattering detection of three α1-adrenoceptor antagonists coupled with high performance liquid chromatograph.

Herein, a Rayleigh light-scattering (RLS) detection method combined with high performance liquid chromatograph (HPLC) without any post-column probe was developed for the separation and determination of three α1-adrenoceptor antagonists. The quantitative analysis is benefiting from RLS signal enhancement upon addition of methanol which induced molecular aggregation to form an hydrophobic interface between aggregates and water that produce a sort of superficial enhanced scattering effect. A good chromatographic separation among the compounds was achieved using a Gemini 5u C18 reversed phase column (250 mm × 4.6 mm; 4 µm) with a mobile phase consisting of methanol and ammonium acetate-formic acid buffer solution (25 mM; pH=3.0) at the flow rate of 0.7 mL min(-1). The RLS signal was monitored at λex=λem=354 nm. A limit of detection (LOD) of 0.065-0.70 µg L(-1) was reached and a linear range was found between peak height and concentration in the range of 0.75-15 µg L(-1) for doxazosin mesylate (DOX), 0.075-3.0 µg L(-1) for prazosin hydrochloride (PRH), and 0.25-5 µg L(-1) for terazosin hydrochloride (TEH), with linear regression coefficients all above 0.999. Recoveries from spiked urine samples were 88.4-99.0% which is within acceptable limits. The proposed method is convenient, reliable and sensitive which has been used successfully in human urine samples.

Metabolism of prazosin in rat and characterization of metabolites in plasma, urine, faeces, brain and bile using liquid chromatography/mass spectrometry (LC/MS).

1. Prazosin, 2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline, is an antihypertensive agent that has been used safely since 1976 and is currently being investigated for the treatment of post-traumatic stress disorder. The in vivo metabolism of prazosin in rat was first reported in 1977, although at the time analytical techniques were not as sophisticated, nor were the mass spectrometers as sensitive, as today. Recently, the in vitro metabolism of prazosin in rat liver microsomes and cryopreserved hepatocytes was investigated using liquid chromatography/mass spectrometry (LC/MS), which revealed new metabolic pathways. 2. In the present work, rat in vivo metabolism was reinvestigated using a quadrupole time-of-flight mass spectrometer coupled with ultra-performance liquid chromatography, or chip-based nanoflow electrospray ionization, with the aim of identifying metabolites revealed by the in vitro studies and any new metabolites. 3. It is reported that prazosin was metabolized in rats to produce the metabolites observed in vitro. In addition, new phase I metabolites, M18, M20 and M21, were formed and conjugation with glucose or taurine formed the new phase II metabolites, M16 and M19, respectively. 4. Evidence for bioactivation of prazosin included detection of ring-opened metabolites (M4 and M7) and a cysteinyl-glycine conjugate (M17). Further support to the structure of the ring-opened metabolite M7 was obtained by nuclear magnetic resonance (NMR) experiments on M7 isolated from urine.

Voltammetric and spectrophotometric techniques for the determination of the antihypertensive drug Prazosin in urine and formulations.

A sensitive method was developed to determine Prazosin using a nafion modified carbon paste electrode (NMCPE). Prazosin was accumulated at a potential of 750 mV in Britton-Robinson buffer (pH 6.0) and then a negative sweep was made obtaining a cathodic peak close to 0 V. Cyclic voltammetric studies indicated that the process was quasi-reversible, and fundamentally controlled by adsorption. To obtain a good sensitivity, the instrumental and accumulation variables were studied using differential pulse voltammetry (DPV). Adsorptive voltammetric peak currents showed a linear response for Prazosin concentrations in the range between 4.0 x 10(-11) and 4.0 x 10(-8) M with two different slopes, and a detection limit (LOD) of 3.1 x 10(-11)M was obtained. The variation coefficient (CV) for a 8.0 x 10(-10) M solution (n = 10) was 4.08%. A spectrophotometric study of Prazosin was also carried out and two absorption bands were obtained at 246 and 329 nm (pH 1.8). The band at 329 nm was pH-dependent and its height and position changed with the pH values, so this allowed the pK'a determination (7.14 +/- 0.20) using different methods. The detection limit reached by means of UV-spectrophotometry was 0.9 x 10(-7) M, and the variation coefficient for 1.5 x 10(-5) M Prazosin solutions was 1.14% (n = 10). Although the sensitivity of the UV-spectrophotometric method was lower than that obtained using adsorptive stripping-differential pulse voltammetry (AdS-DPV), it could be applied to the determination of Prazosin in Minipres tablets. The voltammetric method was used for the determination of the drug in human urine samples at trace levels with good recoveries.

Disinergia urinaria en niños sin neuropatía: tratamiento con prazosín / Urinary dyssinergy in children without neuropathy: treatment with prazosin

La disinergia detrusor-esfínter es un cuadro bien conocido en el paciente neurópata. En nuestra consulta hemos encontrado entre julio 1984 y junio 1995 un grupo de 32 niños sin neuropatía, pero con patrón urodinámico de disinergia. Estos niños fueron tratados con prazosín, un bloqueador alfa, de acuerdo con el siguiente protocolo: el niño se hospitalizó durante 2 semanas. En la primera el grupo recibió un placebo llevándose registro de cifras tensionales y patrón de micción. La segunda semana recibió el prazosín en dosis de 0,05 mg/día manteniendo iguales controles. Antes del alta se realizó nueva urodinamia para luego seguir el tratamiento ambulatorio por 4-6 meses. Los resultados se catalogaron como: excelentes, al desaparecer el patrón disinérgico y toda manifestación clínica; buenos, cuando desapareció el patrón anormal pero hubo alguna sintomatología y malos, en cualquier otro casi durante un período de control de 12-18 meses. Obtuvimos excelentes resultados en 51,61 por ciento y buenos en 29,03 por ciento. Ningún niño mostró hipotensión, pero en 3 casos hubo que suspender el tratamiento por aparición de cefalea o malestar general. Nuestros resultados demuestran que el niño puede presentar una disinergia vesicoesfinteriana aun en ausencia de neuropatía. El prazosín se muestra como una droga efectiva en el tratamiento de estos casos con escasos efectos colaterales

Clinical pharmacokinetics of prazosin.

Prazosin, a quinazoline derivative, is a peripheral vasodilator used in the treatment of arterial hypertension and more recently, congestive heart failure (CHF). Prazosin is extensively metabolised by the liver and has high first-pass metabolism and low oral bioavailability. In normal healthy volunteers, the time of peak concentration occurs between 1 and 3 hours after oral administration, with wide interindividual variations. The extent of oral absorption seems to be similar for different pharmaceutical forms and is not influenced by the presence of food in the digestive tract. Oral bioavailability of prazosin ranges from 43.5 to 69.3% (mean 56.9%). Prazosin is highly (92 to 97%) bound to human plasma proteins (albumin and alpha 1-acid glycoprotein) and the extent of binding is independent of the plasma concentration of the drug in the range of 20 to 150 ng/ml. Preliminary studies in humans indicate that pathways for biotransformation of prazosin are similar to those observed in the rat and dog. Only 6% of prazosin is excreted unchanged, mainly in the urine. The two main metabolites (0-demethylated) are almost completely excreted in bile. The time course of disappearance of prazosin from plasma after intravenous injecton indicates that prazosin disposition should be described by a model containing at least 2 kinetically distinct compartments. The mean elimination half-life is about 2.5 hours. After intravenous administration, the steady-state volume of distribution has been calculated to be 42.2 +/- 8.9L and the total body clearance 12.7 +/- 1.3L/h. In hypertensive patients with normal renal function, prazosin kinetics do not differ significantly from normals. However, prazosin disposition is modified in chronic renal failure and in congestive heart failure. In both cases, the plasma free fraction of prazosin is increased and plasma elimination half-life is longer. Prazosin kinetics may be expected to be altered in patients with liver diseases. Pharmacokinetic data do not suggest a mechanism to explain the disappearance of the first-dose effect during continued administration of prazosin. Although more investigation is needed to define prazosin kinetics in congestive heart failure and chronic renal failure, the available information about prolongation of elimination half-life, decreased protein binding and increased peak plasma concentrations suggest that prazosin dosage should be titrated cautiously in such patients.