Flow-injection spectrophotometric determination of methyldopa in pharmaceutical formulations

A flow-injection spectrophotometric procedure is proposed for methyldopa determination in pharmaceutical preparations. The determination is based on formation of a yellow product (measured at 410 nm) after complexation of methyldopa with molybdate. Under optimal conditions, Beer's law is obeyed in a concentration range of 50-200 mg l⁻¹ methyldopa. Typical correlation between absorbance and analyte concentration was 0.9999. Usual excipients used as additives in pharmaceuticals do not interfere with the proposed method. The analytical frequency was 210 h⁻¹ and the relative standard deviation (R.S.D.) was ≤2% for sample solution containing 150 mg l⁻¹ methyldopa (n = 11). The analytical results obtained in commercial formulations by applying the proposed FIA method were in good agreement with labeled values and those obtained by the Brazilian Pharmacopoeia procedure at 95% confidence level.     

Capillary and microchip electrophoresis of basic drugs with contactless conductivity detection

The extension of contactless conductivity detection in electrophoresis to the determination of basic drugs is demonstrated using beta-adrenergic blocking agents (beta-blockers) and other physiologically active amines as examples. The high-voltage approach to conductivity detection was employed for conventional capillaries as well as microchip devices. Acidic buffers were used in all cases. A buffer consisting of 100 mM acetic acid and 1 mM histidine was deemed most optimal for the separation of six beta-blockers and best results for the analysis of the other amines were achieved with a 20 mM lactic acid buffer at low pH-value. The detection limits ranged from 0.06 to 5 microM. To demonstrate potential practical applications, a main component assay was conducted for three pharmaceutical formulations. On-chip, five pharmaceutical amines could be baseline-resolved in a 8 cm long microchannel in 90 s, albeit a reduced sensitivity and peak capacity compared to conventional capillary electrophoresis.     

Selective spectrophotometric determination of phenolic β-lactam antibiotics in pure forms and in their pharmaceutical formulations

Four simple and selective spectrophotometric methods were developed for the quantitative determination of some phenolic β-lactam antibiotics (amoxicillin trihydrate, cefoperazone sodium, cefadroxil monohydrate, and cefprozil anhydrous) in pure forms as well as in their pharmaceutical formulations through their nitration and subsequent complexation with an nucleophilic reagent (method I), nitrosation and subsequent metal chelation (method II), coupling with diazo reagent (method III), and reaction with copper and extraction of the resulting chelate into chloroform (method IV). The reaction conditions were studied and optimized. Beer’s plots were obeyed in a general concentration range of 5-30 ug ml⁻¹ with correlation coefficients not less than 0.9997 for the four drugs. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets, and suspensions with good recovery; percentage ranged from 99.0 (±1.42) to 100.2 (±1.25) in method I, 99.0 (±0.82) to 100.5 (±0.92) in method II, 99.5 (±0.09) to 100.8 (±0.98) in method III, and 99.3 (±0.01) to 100.2 (±0.05) in method IV. Interferences from other antibiotics and additives were investigated.     

Voltammetric determination of N-acetylcysteine using a carbon paste electrode modified with copper(II) hexacyanoferrate(III)

The preparation and electrochemical characterization of a carbon paste electrode modified with copper(II) hexacyanoferrate(III) (CuHCF) as well as its behavior as electrocatalyst toward the oxidation of N-acetylcysteine were investigated. The electrochemical behavior of the modified electrode and the electrooxidation of N-acetylcysteine were explored using sweep linear voltammetry. The best voltammetric response was observed for a paste composition of 20% (w/w) copper(II) hexacyanoferrate(III) complex, acetate buffer solution at pH of 6.0 as the electrolyte and scan rate of 10 mV s^− 1. A linear voltammetric response for N-acetylcysteine was obtained in the concentration range from 1.2 × 10^− 4 to 8.3 × 10^− 4 mol L^− 1, with a detection limit of 6.3 × 10^− 5 mol L^− 1. The proposed electrode is useful for the quality control and routine analysis of N-acetylcysteine in pharmaceutical formulations.     

Clinical pharmacokinetic data of racemic drugs obtained by the indirect method following precolumn diastereomer formation: is the influence of racemization during chiral derivatization significant?

This report reviews the stereoselective data of a number of racemic drugs (n = 17) obtained from indirect chiral method (via diastereomer formation) in comparison to similar data generated by the application of a direct chiral method. While it was noted that the indirect method still continued to be used to characterize the stereoselective disposition of racemic drugs, the present review critically evaluates the issue of racemization that has the potential to skew the stereoselective data obtained from the indirect method. The review describes various remedies to counter and/or minimize the impact of racemization on the final outcome of the stereoselective analysis by the indirect method. On the basis of this review it could be concluded that the indirect method is a viable and important tool for gathering stereoselective data of racemic drugs used in medical practice as well for those racemic drugs still in discovery and developmental stages.     

Assay of acebutolol in pharmaceuticals by analytical capillary isotachophoresis

Acebutolol [N-{3-acetyl-4-[(2-hydroxy-3-(isopropylamino)propoxy]phenyl} butanamide] is a cardioselective beta-blocker with a potent anti-hypertensive and antiarrhythmic effect. The optimised operational system of electrolytes for the newly developed ITP separation of acebutolol consisted of 10mM potassium acetate +10mM acetic acid (pH 4.65) as the leading electrolyte and 10mM beta-alanine with pH approximately 4 (adjusted with acetic acid) as the terminating electrolyte. The driving and detection currents were 75 and 20 microA, respectively and the analysis took approximately 13 min. Under these conditions the effective mobility of acebutolol was determined as 20.7 x 10(-9) m2 V(-1) s(-1). The calibration dependence was rectilinear in the range 0.14-1.4 mg ml(-1) of acebutolol base (r = 0.9995); relative standard deviation (RSD) values were 1.1% and 1.2% (n = 6) when determining 0.42 and 0.98 mg ml(-1) of acebutolol in a pure standard solution. The method, with the limit of detection (LOD) of 0.04 mg ml(-1) and limit of quantification (LOQ) of 0.12 mg ml(-1), was applied to the assay of acebutolol in Sectral tablets, Acecor tablets, Apo-acebutol tablets (nominal content 400 mg of acebutolol per tablet) and Acebirex tablets (nominal content 200 mg of acebutolol per tablet) with RSD = 0.7-1.7% (n = 6). No interference from any excipients present in the tablets was observed. The recoveries ranged from 98.8% to 102.4% as found by the standard addition technique.     

Electrochemical determination of prolintane in pharmaceutical formulations and in human urine

The oxidative behavior of 1-[1-(phenylmethyl)butyl]pyrrolidine, prolintane, was studied at a glassy carbon electrode using linear-sweep and differential-pulse voltammetry. The oxidation process was shown to be irreversible using 0.04 M Britton–Robinson buffer and was diffusion-adsorption controlled. Two voltammetric methods were developed for the determination of prolintane using different techniques: linear-sweep and differential-pulse voltammetry. The peak current varied linearly with prolintane concentrations in the range of 1.0 × 10⁻⁵ −2.5 × 10⁻⁴ M, with a detection limit of 8.5 × 10⁻⁶ and 4.0 × 10⁻⁶ M, and with relative standard deviations of 2.1 % and 3.1 %, respectively. The methods were applied to commercial preparations, giving relative errors less than 3.1 % and relative standard deviations lower than 4.8 % (n = 10). Determination of prolintane (down to the 8.5 × 10⁻⁸ M level) can be performed by using a preconcentration step prior to the determination by differential-pulse voltammetry in 0.04 M Britton–Robinson buffer (pH 8.0) with preconcentration potential of 0.0 V. The detection limit was found to be 6.2 × 10⁻⁸ M (4 min preconcentration) and the relative standard deviation for 2.5 × 10⁻⁷ M prolintane (n = 5) was 4.6 %. Applicability to human urine analysis is illustrated (recovery 98 ± 2 %). Standard additions method can be used to determine prolintane in real samples of urine.     

Diels-alder reactions of substituted maleic anhydrides with 1-vinylcoclohexane: Stereospecific formation of a bicyclic intermediate useful for syntheses of clerodane diterpenes

The Diels-Alder reaction of 1-vinylcyclohexene with aconitic anhydride gives the adduct 5b which has the reversed stereochemistry of that predicted by Alder's endo rule. On the other hand, reactions with chloromethylmaleic anhydride and citraconic anhydride afford endo-adducts 23 and 24, respectively. Adduct 23 has the appropriate stereochemistry and functionality for the syntheses of clerodane and related diterpenes.     

Two- and three-way chemometrics methods applied for spectrophotometric determination of lorazepam in pharmaceutical formulations and biological fluids

In this work, direct determination of lorazepam, an anxiolytic and sedative agent, in pharmaceutical formulations and biological fluids (urine and human plasma) was accomplished based on ultraviolet spectrophotometry (260-380 nm) using parallel factor analysis (PARAFAC) and partial least squares (PLS). The study was carried out in the pH range from 1.0 to 12.0 and with a concentration range from 0.50 to 8.75 μg ml⁻¹ of lorazepam. Multivariate calibration models using PLS at different pH and PARAFAC were elaborated for ultraviolet spectra deconvolution and lorazepam quantitation. The best models for the system were obtained with PARAFAC and PLS at pH = 2.05 (PLS-PH2). The capabilities of the method for the analysis of real samples were evaluated by determination of lorazepam in pharmaceutical preparations and biological (urine and plasma) fluids with satisfactory results. The accuracy of the method, evaluated through the root mean square error of prediction (RMSEP), was 0.0429 for lorazepam with best calibration curve by PARAFAC and 0.0467 for lorazepam with PLS model at best pH. The protolytic equilibria of lorazepam at 25 °C and ionic strength of 0.1 M have also been determined spectrophotometrically. Protolytic equilibria of lorazepam were evaluated by DATAN program using the corresponding absorption spectra-pH data. The obtained pK_a values of lorazepam are 1.54 and 11.61 for pK_a1 and pK_a2, respectively.     

Simultaneous determination of allantoin, choline and L-arginine in Rhizoma Dioscoreae by capillary electrophoresis

A rapid, easy and reproducible capillary electrophoresis (CE) method for the simultaneous determination of allantoin, choline and arginine in Rhizoma Dioscoreae was developed first time. Under the optimum condition, the three analytes could be well separated within 5 min in a 70 cm (60 cm effective length) x 75 microm i.d. capillary. The relative standard deviations for both migration time and peak height were less than 3.20%. The linear response range was 5.0-150, 0.9-100 and 1.0-200 microg/ml for arginine, choline and allantoin, respectively. The detection limit of three components was 2.0, 0.4 and 0.5 microg/ml for arginine, choline and allantoin, respectively. Contents of arginine, choline and allantoin in the crude drug of Rhizoma Dioscoreae could be easily determined by the proposed method with satisfactory results.