Enantiomeric separation and quantitative determination of propranolol enantiomers in pharmaceutical preparations by chiral liquid chromatography

Neste trabalho é descrito um método validado empregando a cromatografia líquida de alta eficiência com fase estacionária quiral para a separação e determinação quantitativa dos enantiômeros do propranolol em formulações farmacêuticas. A separação foi obtida em meio orgânico polar empregando a coluna ±-Burke 2® como fase estacionária quiral (250 x 4,6 mm, 5 µm) e fase móvel constituída por diclorometano: metanol (90:10 v/v) juntamente com 12 mM de acetato de amônio e vazão de 0,9 mL/min. A detecção foi efetuada por absorção no ultravioleta a 280 nm. Em todos casos o tempo de corrida foi menor do que 10 min. O coeficiente de correlação obtido pelo método de regressão linear foi de 0,9995 para o R-prop e de 0,9998 para o S-prop. A precisão intra-dia, expressa como desvio padrão relativo, foi menor do que 2%. A exatidão, determinada pela recuperação média de R- e S-prop nas amostras foi de 97,3% e 100,1% para a amostra comercial e de 99,5% e 100,4% para a amostra simulada, respectivamente. Excelentes níveis para os limites de detecção (1,34 ng) e de quantificação (4,47 ng), além do tempo rápido de eluição dos enantiômeros do propranolol, confirmam a aplicabilidade do método no controle de qualidade de preparações farmacêuticas contendo este fármaco.This paper describes validated direct liquid chromatographic chiral methods for enantiomeric separation and quantitative determination of clinically significant ²-blocking agent, propranolol. A liquid chromatographic method was validated and applied for enantiomeric determination of propranolol enantiomers in pharmaceutical formulations. Separation were obtained in polar organic mode on a ±-Burke 2® chiral stationary phase (250 x 4.6 mm, 5µm) with mobile phase composed of dichloromethane:methanol (90:10 v/v), along with 12 mM of ammonium acetate, at a flow rate of 0.9 mL/min. Detection was made by ultraviolet absorption at 280 nm. In all cases the run time was less than 10 min. The correlation coefficient for linear regression curves of R-propranolol and S-propranolol were 0.9995 and 0.9998 respectively. The intra-day precision, expressed as RSD was less than 2%. The accuracy determined by average recovery of R-propranolol and S-propranolol from sample matrices were 97.3% and 100.1% in commercial sample and 99.5% and 100.4% in simulated samples, respectively. Excellent levels of limit of detection (mean value = 1.34 ng) and limit of quantitation (mean value = 4.47 ng), along with rapid elution time of both enantiomers, makes the method useful for routine enantiomeric quality control applications

High throughput simultaneous assay of atenolol and chlortalidone in combined dose tablets by liquid chromatography and capillary zone electrophoresis

New fast liquid chromatographic and capillary zone electrophoresis methods were developed and validated for simultaneous determination of atenolol and chlortalidone in combined dose tablets. The reversed phase HPLC method was carried out on a CN LiChrosorb® (125 x 4 mm, 5 μm) column. The CZE method was carried out on an uncoated fused-silica capillary of 30 cm x 75 μm i.d. with 25 mmol L-1 sodium tetraborate, pH 9.4. The total analysis time was <6 and <2.5 min for HPLC and CZE methods, respectively. Both methods can be used for stability studies as well.Colegio de Farmacéuticos de la Provincia de Buenos Aire

UV-Derivative Spectrophotometric and Stability-Indicating High-Performance Liquid Chromatographic Methods for Determination of Simvastatin in Tablets

A stability-indicating high-performance liquid chromatographic (HPLC) and a second-order derivative spectrophotometric (UVDS) analytical methods were validated and compared for determination of simvastatin in tablets. The HPLC method was performed with isocratic elution using a C18 column and a mobile phase composed of methanol:acetonitrile:water (60:20:20, v/v/v) at a flow rate of 1.0 ml/min. The detection was made at 239 nm. In UVDS method, methanol and water were used in first dilution and distilled water was used in consecutive dilutions and as background. The second-order derivative signal measurement was taken at 255 nm. Analytical curves showed correlation coefficients > 0.999 for both methods. The quantitation limits (QL) were 2.41 mu g/ml for HPLC and 0.45 mu g/ml for UVDS, respectively. Intra and inter-day relative standard deviations were < 2.0 %. Statistical analysis with t- and F-tests are not exceeding their critical values demonstrating that there is no significant difference between the two methods at 95 % confidence level.CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil