Hydrolytic degradation of nitrendipine and nisoldipine.

The development of a new HPLC-UV diode array procedure applied to follow the hydrolytic degradation of two well-known 4-nitrophenyl-1,4-dihydropyridine derivatives, nitrendipine and nisoldipine is reported. Hydrolysis of each drug were carried out in ethanol/Britton-Robinson buffer at different pHs, stored into amber vials at controlled temperatures of 40, 60 and 80 degrees C and periodically sampled and assayed by HPLC. Nitrendipine degradation in different parenteral solutions was also evaluated. The HPLC procedure exhibited an adequate selectivity, repeatability (<1%) and reproducibility (<2%). The recoveries were higher than 98% with CV of 1.13 and 1.54% for nitrendipine and nisoldipine, respectively. A significant degradation was observed at alkaline pH (>pH 8) with a first order kinetic for both drugs. At pH 12, 80 degrees C, k values of 3.56x10(-2) x h(-1) and 2.22x10(-2) for nitrendipine and nisoldipine, respectively were obtained. Also, activation energies of 16.8 and 14.7 kcal x mol(-1) for nitrendipine and nisoldipine, respectively, were calculated. Furthermore, from the results obtained from hydrolytic degradation in different solutions for parenteral use, we can affirm that solutions significantly increased the degradation of nitrendipine. In conclusion, the HPLC proposed procedure exhibited adequate analytical requirements to be applied to the hydrolytic degradation studies of nitrendipine and nisoldipine. Furthermore, all tested parenteral solutions significantly increased the hydrolytic degradation of nitrendipine, the composition of solution being a relevant factor.

A selective HPLC method for determination of lercanidipine in tablets.

An HPLC reversed phase method using both UV (356 nm) and electrochemical (1000 mV) detection was developed in order to determine lercanidipine in commercial tablets. Repeatability and reproducibility were adequate. For quantification we have used the calibration plot method for lercanidipine concentration ranging between 1 x 10(-5) and 1 x 10(-4) M. Also, the proposed method is sufficiently selective to distinguish the parent drug and the degradation products after hydrolysis, photolysis or chemical oxidation. Furthermore, the typical excipients included in the drug formulation (talc, lactose, cornstarch, microcrystalline cellulose, carboxymethylcellulose and magnesium stearate) do not interfere with the selectivity of the method. Finally, the proposed chromatographic method was successfully applied to the quantitative determination of lercanidipine in commercial tablets.

Electrochemical study of nisoldipine: analytical application in pharmaceutical forms and photodegradation.

The anodic and cathodic behavior of nisoldipine, 3-isobutyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)pyridine-3 ,5-dicarboxylate, are reported. This drug belongs to the nitroaryl-1,4-dihydropyridine family, known as calcium channel antagonist and employed in therapeuticalls as peripheral and cerebral vasodilators, in the treatment of the arterial hypertension. The cathodic response corresponds to the reduction of the nitroaromatic group to generate the hydroxylamine derivative. The study by dc and d.p.p. reveals the appearance of four signals depending on pH: Signal I (pH 1-11.5) R - NO2 + 4H+ + 4e- --> R - NHOH + H2O; Signal II (pH 1-5) R - N+H2OH + 2H+ + 2e- --> RN+H3 + H2O; Signal III (pH > 11.5) R - NO2 + e- <--> R - NO2.-; Signal IV (pH > 11.5) R - NO2.- + 3e- + 4H+ --> R - NHOH. In contrast, the anodic response corresponds to the oxidation of the 1,4-dihydropyridine ring to generate the corresponding pyridine derivative. Both, cathodic (d.p.p.) and anodic signals (d.p.v.) were employed to develop analytical methodology for the determination of the drug. The repeatability of the measurements for both methods was adequate with R.S.D. of 1.4% (n = 10) and 2.1% (n = 10) for d.p.p. and d.p.v., respectively. Also recovery studies, 103.8% (R.S.D. 2.65%) by d.p.p. and 98.7% (R.S.D. 2.1%) by d.p.v. show that the accuracy and precision of the developed methods were adequate. The analytical methods were successfully applied to the determination of nisoldipine in both tablets and capsules. In addition, a preliminary study of the photostability of nisoldipine (using both UV and artificial day light) was completed. The identity of the main electroactive photodegradation products by GC with spectrometry detection is provided.

Voltammetric behavior and analytical applications of lomefloxacin, an antibacterial fluorquinolone.

Lomefloxacin was reduced on a dropping mercury electrode, producing one or more peaks, depending on the pH of the aqueous medium. Coulometric measurements gave an experimental value of 1 electron for the main peak. Electrolysis was followed by UV spectrophotometry and liquid chromatography (LC), showing that a new band at 413 nm appeared for the electrolysis product in an acidic medium. Furthermore, by using UV spectrophotometry, an apparent pKa value of 6.75 +/- 0.05 was obtained for lomefloxacin corresponding to the carboxyl moiety in the 3-position. For analytical studies, the differential pulse polarographic mode in 0.1 N HCl was selected. The repeatability and reproducibility of the method were adequate (coefficient of variation [CV], 0.51%). The calibration curve method was used for the lomefloxacin concentration range of 7.0 x 10(-6) to 7.0 x 10(-5)M. The detection and quantitation limits were 1.0 x 10(-6) and 6.9 x 10(-6)M, respectively. For purposes of comparison, both UV spectrophotometric and LC (with UV and fluorimetric detection) methods were developed. The polarographic method showed good selectivity with respect to both excipients and degradation products. The recovery study showed a CV of <2% and an average recovery of 99.5% and it was not necessary to treat the sample before analysis. The method was applied to the determination of the uniformity content of lomefloxacin commercial tablets. The polarographic method was also successfully applied to the quantitation of lomefloxacin in urine, and the renal excretion profile was also determined.

Voltammetric behavior of naratriptan and its determination in tablets.

The electrochemical behavior and the analytical application of the selective serotonin agonist naratriptan (N-methyl-3-(1-methyl-4-piperidyl)indole-5-ethanesulfonamide) are presented herein. Naratriptan exhibits an anodic response in aqueous media over a broad pH range (pH 2-12), as determined by differential pulse voltammetry and cyclic voltammetry using glassy carbon electrodes. This response is irreversible in nature, diffusion-controlled and probably caused by the oxidation of the naratriptan indole moiety. The differential pulse voltammetry technique was performed in 0.1 mol L(-1) Britton-Robinson buffer (pH=3), which elicited the most reproducible results. The percentage of naratriptan recovery was 102.1+/-1.8%, and the limits of detection and quantitation were 9.5x10(-6) and 2.0x10(-5) mol L(-1), respectively. Selectivity trials revealed that the oxidation signal of the drug was not disturbed by the presence of excipients or degradation products. Thus, we conclude that the method presented herein is useful for the quantification of naratriptan in pharmaceutical drugs and that this method requires no separations or extractions. Finally, this voltammetric method was successfully applied to determine the quantity and the content uniformity of naratriptan in drug tablets. A comparison of this technique to the standard high-performance liquid chromatography technique was conducted at the end of our study.

Electrochemical behavior of atomoxetine and its voltammetric determination in capsules.

In this work, the electrochemical behavior and the analytical application of atomoxetine, a selective noradrenaline reuptake inhibitor, are studied. Atomoxetine, studied by differential pulse voltammetry and cyclic voltammetry on a glassy carbon electrode, exhibited an anodic response in aqueous media with pH between 1.5 and 7. In non-aqueous medium (acetonitrile), the drug exhibited two irreversible oxidation peaks that are diffusion controlled. From chronocoulometric studies in acetonitrile, it was determined that each oxidation signal involves two and four electrons, respectively. For analytical purposes, a differential pulse voltammetry technique in 0.1 mol L(-1) perchloric acid was selected, which exhibited adequate figures of merit. The percent recovery was 96.6+/-1.2 and the detection and quantitation limits were 6.9 x 10(-5) and 1.0 x 10(-4) mol L(-1), respectively. Also, results indicate that excipients do not interfere with the oxidation signal of atomoxetine, which leads to the conclusion that the developed method is satisfactorily selective for atomoxetine quantification in pharmaceuticals with no prior separation or extraction necessary. Finally, the proposed voltammetric method was successfully applied to both the assay and the uniformity content of atomoxetine in capsules. For comparison, high-performance liquid chromatography analysis was also performed.

Simultaneous voltammetric determination of levodopa, carbidopa and benserazide in pharmaceuticals using multivariate calibration.

An analytical methodology based on differential pulse voltammetry (DPV) on a glassy carbon electrode and the partial least-squares (PLS-1) algorithm for the simultaneous determination of levodopa, carbidopa and benserazide in pharmaceutical formulations was developed and validated. Some sources of bi-linearity deviation for electrochemical data are discussed and analyzed. The multivariate model was developed as a ternary calibration model and it was built and validated with an independent set of drug mixtures in presence of excipients, according with manufacturer specifications. The proposed method was applied to both the assay and the uniformity content of two commercial formulations containing mixtures of levodopa-carbidopa (10:1) and levodopa-benserazide (4:1). The results were satisfactory and statistically comparable to those obtained by applying the reference Pharmacopoeia method based on high performance liquid chromatography. In conclusion, the methodology proposed based on DPV data processed with the PLS-1 algorithm was able to quantify simultaneously levodopa, carbidopa and benserazide in its pharmaceuticals formulations using a ternary calibration model for these drugs in presence of excipients. Furthermore, the model appears to be successful even in the presence of slight potential shifts in the processed data, which have been taken into account by the flexible chemometric PLS-1 approach.

Electrochemical study and analytical applications for new biologically active 2-nitrophenylbenzimidazole derivatives.

The present study addresses the electrochemical behavior and the analytical applications of six 2-nitrophenylbenzimidazole derivatives with activity against Trypanosoma cruzi. When studied in a wide range of pH, by differential pulse polarography, tast polarography and cyclic voltammetry, these compounds exhibited two irreversible cathodic responses. With analytical purposes, the differential pulse polarography mode was selected, which exhibited adequate analytical parameters of repeatability, reproducibility and selectivity. The percentage of recovery was in all cases over 99%, and the detection and quantitation limits were at the level of 1 x 10(-7)mol L(-1) and 1 x 10(-6)mol L(-1), respectively. In addition, the differential pulse polarography method was successfully applied to study the hydrolytic degradation kinetic of one of the tested compounds. Activation energy, kinetic rate constants at different temperatures and half-life values of such application are reported.

Voltammetric reduction of finasteride at mercury electrode and its determination in tablets.

Finasteride in hydroalcoholic solutions (ethanol/Britton-Robinson buffer, 30/70) exhibits cathodic response in a wide range of pH (-0.5 to 12) using differential pulse (DPP) and test polarography (TP). The reduction peak of finasteride at acidic pH, is a catalytic proton peak resulting from a mechanism involving a first protonation of finasteride followed by the reduction of the protons combined with finasteride in order to regenerate finasteride and liberate hydrogen. Based on the catalytic hydrogen wave, a novel method for the determination of finasteride can be proposed. For analytical purposes we selected DPP technique in an ethanol/0.0625 mol L(-1) H(2)SO(4) (30/70) solution medium. In this condition the I(p) varied linearly with finasteride concentration between 5 x 10(-5) and 5 x 10(-4) mol L(-1). Within-day and inter-day reproducibility's were adequate with R.S.D. values lower than 2%. The selectivity of the method was checked with both accelerated degradation trials and typical excipients formulations. The developed method was applied to the assay and the uniformity content of finasteride tablets and compared with the standard HPLC method. The DPP-developed method was adequate for the finasteride determination in pharmaceutical forms as that exhibited an adequate accuracy, reproducibility and selectivity. Furthermore, treatment of the sample was not required as in HPLC; the method is not time-consuming and less expensive than the HPLC ones.

Voltammetric behaviour of bromhexine and its determination in pharmaceuticals.

A complete electrochemical study and a novel electroanalytical procedure for bromhexine quantitation are described. Bromhexine in methanol/0.1molL(-1) Britton-Robinson buffer solution (2.5/97.5) shows an anodic response on glassy carbon electrode between pH 2 and 7.5. By DPV and CV, both peak potential and current peak values were pH-dependent in all the pH range studied. A break at pH 5.5 in E(P) versus pH plot revealing a protonation-deprotonation (pK(a)) equilibrium of bromhexine was observed. Spectrophotometrically, an apparent pK(a) value of 4.3 was also determined. An electrodic mechanism involving the oxidation of bromhexine via two-electrons and two-protons was proposed. Controlled potential electrolysis followed by HPLC-UV and GC-MS permitted the identification of three oxidation products: N-methylcyclohexanamine, 2-amino-3,5-dibromobenzaldehyde and 2,4,8,10-tetrabromo dibenzo[b,f][1,5] diazocine. DPV at pH 2 was selected as optimal pH for analytical purposes. Repeatability, reproducibility and selectivity parameters were adequate to quantify bromhexine in pharmaceutical forms. The recovery was 94.50+/-2.03% and the detection and quantitation limits were 1.4x10(-5) and 1.6x10(-5)molL(-1), respectively. Furthermore, the DPV method was applied successfully to individual tablet assay in order to verify the uniformity content of bromhexine. No special treatment of sample were required due to excipients do not interfered with the analytical signal. Finally the method was not time-consuming and less expensive than the HPLC one.