Adriana Ines Segall

Design, synthesis and antitumoural activity of trisubstituted dihydrobenzo[a]carbazoles

Summary The design, synthesis, binding affinities for rabbit uterus estrogen receptors and in vivo action of two trisubstituted dihydrobenzo[ a ]carbazoles are reported. Relative binding affinities were similar to tamoxifen. In vivo studies in rats bearing NMU-induced mammary tumours indicate that tamoxifen (200 μg sc daily) led to 51.6% tumour regression, ovariectomy to 54.4%, and derivatives 6 and 7 (200 μg sc daily) to 50.0 and 54.8%, respectively. These experiments demonstrated that derivatives 6 and 7 are as effective as tamoxifen in the model studied.

REVERSED-PHASE HPLC DETERMINATION OF SILDENAFIL CITRATE IN THE PRESENCE OF ITS OXIDATIVE-INDUCED DEGRADATION PRODUCTS

The determination of sildenafil citrate in the presence of its oxidative-induced degradation products by reversed-phase HPLC is described. The method was validated as stability-indicating by forced decomposition of sildenafil citrate in acid, base, oxidative, thermal, and photochemical media. The chromatographic conditions employed a reversed-phase C18 column (LiChrospher, 5 μm, 25 cm × 4.6 mm) isocratic elution with 70 mM potassium phosphate monobasic containing 100 mM triethylamine (pH 3.0)-ACN (70:30, v/v) and ultraviolet (UV) detection at 225 nm. The peak area versus sildenafil citrate concentration proved linear over the 10–160% range of the working analytical concentration of 0.5-mg/mL. Mean absolute recovery of sildenafil citrate using the described method was 100.9 ± 1.1 % (mean ± SD, n = 9). The precision, expressed as relative standard deviation (RSD), of ten replicate injections of sildenafil citrate reference solution, remained below 0.51 %.

Validation of an HPLC Method for the Determination of Valacyclovir in Pharmaceutical Dosage

Abstract A new analytical method was developed together with its validation study, by means of a high resolution liquid chromatography (HPLC) of reverse phase to quantify valacyclovir L‐Valine, ester with 9‐[(2‐hydroxyethoxy)methyl]guanine hydrochloride in tablets. Determination was carried out by means of an ODS C18 column (Microsorb‐MV™100 A, 10 µm, 25 cm × 4.6 mm); the mobile phase consisted of acetic acid in water (1∶1000)∶methanol (70∶30). It was pumped through the chromatographic system at a flow rate of 1.0 mL/min. The UV detector was operated at 254 nm. The validation study was carried out fulfilling the ICH guidelines in order to prove that the new analytical method meets the reliability characteristics, and these characteristics show the capacity of an analytical method to keep, throughout the time, the fundamental criteria for validation: selectivity, linearity, precision, accuracy, and sensitivity. The method is applied during the working day for the quality control of commercial valacyclovir tablets in order to quantify the drug and to check the uniformity content test.

Development and validation of a reversed-phase liquid chromatographic method for analysis of estradiol valerate and medroxyprogesterone acetate in a tablet formulation.

A simple and accurate liquid chromatographic method was developed for estimation of estradiol valerate and medroxyprogesterone acetate in pharmaceuticals. Drugs were chromatographed on a reverse phase C18 column, using a mixture (30:70) of ammonium nitrate buffer and acetonitrile and eluants monitored at a wavelength of 280 nm. Solution concentrations were measured on a weight basis to avoid the use of an internal standard. The method was statistically validated for its linearity, accuracy, precision and selectivity. Due to its simplicity and accuracy, the authors believe that the method may be used for routine quality control analysis. It does not require any specific sample preparation except the use of a column guard before the analytical column and suitable prefilter attached to the syringe prior to injection.

A STABILITY-INDICATING HPLC METHOD TO DETERMINE FINASTERIDE IN A TABLET FORMULATION

ABSTRACT A simple high performance liquid chromatographic method was developed for simultaneous determination of finasteride and its degradation products. HPLC analysis was carried out using a C18 column and methanol:water (70 : 30) as the mobile phase. Detection was carried out at 210 nm using a flow rate of 1.0 mL per min. Finasteride was eluted at 6 min. Standard deviation values were below 2%. The method was validated as stability-indicating by forced decomposition of finasteride using acid, base, hydrogen peroxide, heat, and light. Chromatograms showed good resolution, sensitivity, and no interference of degradation products. The response was linear over the concentration range of 50 to 800 µg/mL, with correlation coefficients of variation greater than 0.9995. Recovery studies gave results between 100 to 103%.

Validated Reversed‐Phase HPLC Method for the Determination of Atenolol in the Presence of Its Major Degradation Product

Abstract A reversed‐phase liquid chromatographic (RP‐LC) assay method, developed for the quantitative determination of atenolol in the presence of its degradation products is described. The assay involved an isocratic elution of atenolol in a Waters µBondapak® C18 column using a mobile phase consisting of acetonitrile‐sodium phosphate monobasic (0.08 M, pH 3.0) (10:90, v/v). The flow rate was 1.0 mL/min and the analyte monitored at 284 nm. The assay method was found to be linear from 0.4 to 12.8 µg injected. All the validation parameters were within the acceptance range. The developed method was successfully applied to estimate the amount of atenolol in tablets.

HPLC analysis of 5H-benzo[a]carbazole with antifungal activity

A sensitive and simple high-performance liquid chromatographic (HPLC) method for the assay of 6,11-dihydro-2-methoxy-5H-benzo[a]carbazole (1) and 6,11-dihydro-2-methoxy-11-[2-(1-piperidinyl)]ethyl-5H-benzo[a]carbazole (2) was developed. The procedure is based on the use of the reversed-phase high-performance liquid chromatographic (RP-HPLC) method with UV detector. Each analysis required no longer than 11 min. A linear relationship between the concentration of both the drugs and the UV absorbance at 254 nm was obtained. This linearity was maintained over the concentration ranged from 5 to 80 microg/ml. The detection limits were found to be 1.6 and 0.7 ng for compounds 1 and 2. The quantitation limits were found to be 5.3 and 2.5 ng for compounds 1 and 2, respectively. For recovery studies, several determinations were carried out. Recovery values ranged from 98 to 102.1% for compound 1 and from 98.4 to 101.6% for compound 2. Method precision was also evaluated and RSD% found was less than 2%. This method was applied without any interference from degradation products.

A Stability-Indicating HPLC Method to Determine Cyproterone Acetate in Tablet Formulations

A simple and accurate liquid chromatographic method was developed to estimate cyproterone acetate (CA) in pharmaceuticals. The drug was chromatographed on a reversed-phase C18 column. Eluents were monitored at a wavelength of 254 nm utilizing a mixture (60:40) of acetonitrile and water. Solution concentrations were measured on a weight basis to avoid the use of an internal standard. The method was statistically validated for linearity, accuracy, precision, and selectivity. Due to its simplicity and accuracy, we believe that the method can be used for routine quality control analysis. No specific sample preparation is required except for the use of a column guard and a suitable prefilter attached to the syringe.

High Performance Liquid Chromatographic Determination of Sodium Cromoglycate

AbstractA simple and precise liquid chromatographic method was developed for the estimation of sodium cromoglycate (SC) in pharmaceuticals. The drug was chroma-tographed on a reverse phase C18 column. The eluants were monitored at a wavelength of 325 nm utilizing a mixture (80:20) of solution A: 0.025 M 1-octane sulfonic acid sodium salt in acetic acid (1:100), and solution B: methanol, aceto-nitrile (3:2). Solution concentrations were measured on a weight basis to avoid the use of an internal standard. The method was statistically validated for its linearity, accuracy, precision, selectivity, limit of detection and limit of quantitation. Due to its simplicity and accuracy, the authors believe that the method can be used for routine quality control analysis. It does not require any specific sample preparation except for the use of a column guard before the analytical column and a suitable profiler attached to the syringe prior to injection.

Validation of an HPLC Method for the Determination of Imatinib Mesylate in Pharmaceutical Dosage

Abstract This paper describes the development and validation of a new, simple, fast, and sensitive liquid chromatographic method for the determination of imatinib mesylate. Imatinib mesylate is not listed in any pharmacopoeia, and there are few methods in the literature for its quantitation in pharmaceutical dosage forms. In this work, a C18 μBondapak® (3.9×150 mm, 5 µm) column was used as the stationary phase, and 30 mM sodium heptane sulphonic acid in 0.01 M KH2PO4 (pH 2.5):MeOH (42:58) was the mobile phase. Detection was performed on a UV detector at 237 nm. Through the evaluation of the analytical parameters, it was shown that the method is linear (r=0.9994) at concentrations ranging from 0.3 mg/mL to 0.8 mg/mL. The relative standard deviation values [RSD] for intra‐ and inter-day precision studies were 1.7 and 2.6. Recoveries ranged between 96.2 and 101.4.