Validation of a high performance liquid chromatographic method for quantitative determination of boldine in fluid extract of boldo

A simple and specific method was validated for quantification of boldine in fluid extract of boldo (Peumus boldus Mol.) using high-performance liquid chromatography. A reversed-phase C18 , Phenomenex® (150 x 4.6 mm, 4 µm) column was employed. The mobile phase consisted of 0.1 % trifluoroacetic acid and acetonitrile (78:22, v/v) at a flow rate of 0.8 mL/min. The column was maintained at 30 °C and the boldine peak detection was performed at a wavelength of 281 nm. The parameters used in the validation process were: linearity, specificity, precision, accuracy, limit of detection, limit of quantification and robustness. The validated method was selective and linear (r≥0.9991) for boldine concentration considering 5.0, 10.0, 15.0, 20.0 and 25.0 micro;g/mL. The recovery ranged from 90.93 % to 96.24 % and the limit of quantification was 2.41 micro;g/mL. The precision determined was reported as RSD (1.73 %). The method can be successfully applied to measure boldine concentrations in Boldo extract and be included in routine analysis of quality control.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Validation of a high performance liquid chromatographic method for quantitative determination of boldine in fluid extract of boldo

A simple and specific method was validated for quantification of boldine in fluid extract of boldo (Peumus boldus Mol.) using high-performance liquid chromatography. A reversed-phase C18 , Phenomenex® (150 x 4.6 mm, 4 µm) column was employed. The mobile phase consisted of 0.1 % trifluoroacetic acid and acetonitrile (78:22, v/v) at a flow rate of 0.8 mL/min. The column was maintained at 30 °C and the boldine peak detection was performed at a wavelength of 281 nm. The parameters used in the validation process were: linearity, specificity, precision, accuracy, limit of detection, limit of quantification and robustness. The validated method was selective and linear (r≥0.9991) for boldine concentration considering 5.0, 10.0, 15.0, 20.0 and 25.0 micro;g/mL. The recovery ranged from 90.93 % to 96.24 % and the limit of quantification was 2.41 micro;g/mL. The precision determined was reported as RSD (1.73 %). The method can be successfully applied to measure boldine concentrations in Boldo extract and be included in routine analysis of quality control.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and validation of a high performance liquid chromatography method for the determination of paracetamol in tablets

Um método simples e sensível por CLAE foi desenvolvido para a determinação quantitativa de paracetamol em comprimidos. Condições cromatográficas para uma eficiente separação foram obtidas empregando-se fase estacionária C8, fase móvel de KH2 PO4 40 mM pH 6,0 e metanol 85:15 (v/v), com fluxo de 1,2 mL/min. A análise de regressão mostrou um coeficiente de correlação superior a 0,99. O método apresentou recuperação consistente para paracetamol (97,03-100,57 %). A precisão intra-dia e precisão intermediária não ultrapassou 1,87 e 0,95 % do CV, respectivamente. O desenvolvimento e a validação do método apresentaram-se adequados para o controle de qualidade de rotina da análise de paracetamol em comprimidos.A simple and sensitive HPLC assay method has been developed for the quantitative determination of paracetamol in tablets. Efficient chromatographic separation was achieved on a C8 stationary phase with mobile phase of KH2 PO4 40 mM pH 6.0 and methanol 85:15 (v/v), at a flow rate of 1.2 mL/min. Regression analysis showed a correlation coefficient greater than 0.99. The method has shown consistent recoveries for paracetamol (97.03-100.57 %). Intra-day and intermediate precision did not exceed 1.87 and 0.95 % of the CV, respectively. The developed and validated method is suitable for the routine quality control analysis of paracetamol in tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Stability-indicating RP-HPLC method for determination of beclomethasone dipropionate in nanocapsule suspensions

A simple stability-indicating RP-HPLC/UV method was validated for determination of beclomethasone dipropionate (BD) in nanocapsule suspensions. Chromatographic conditions consisted of a RP C18column (250 mm x 4.60 mm, 5 µm, 110 Å), using methanol and water (85:15 v/v) as mobile phase at 1.0 mL/min with UV detection at 254 nm. The calibration curve was found to be linear in the concentration range of 5.0-25.0 µg/mL with a correlation coefficient >; 0.999. Precision was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of BD from nanocapsules (98.03% to 100.35%). Specificity showed no interference from the components of nanocapsules or from the degradation products derived from acid, basic and photolytic conditions. In conclusion, the method is suitable to be applied to assay BD in bulk drug and in nanocapsules, and it can be employed to study stability and degradation kinetics.Um método simples de CLAE-FR/UV indicativo de estabilidade foi validado para a determinação do dipropionato de beclometasona (BD) em suspensões de nanocápsulas. As condições cromatográficas foram: coluna C18 fase reversa (250 mm x 4,60 mm, 5 µm, 110 Å), usando como fase móvel metanol e água (85:15 v/v) a 1,0 mL/min, com detecção UV a 254 nm. A curva de calibração foi linear no intervalo de 5,0-25,0 µg/mL com coeficiente de correlação >;0,999. A precisão foi demonstrada por um desvio padrão relativo menor que 2,0%. A exatidão foi avaliada pelo teste de recuperação do BD a partir das nanocápsulas (98,03% a 100,35%). O teste de especificidade não mostrou interferência dos componentes das nanocápsulas e nem dos produtos de degradação derivados de condições ácidas, básicas e fotolíticas. Em conclusão, o método é adequado para ser aplicado na avaliação do BD puro e em nanocápsulas e pode ser empregado para o estudo de estabilidade e degradação cinética

HPLC method for assessment of in vitro and in vivo recovery of gatifloxacin using microdialysis

A simple and sensitive HPLC method was validated for assessment of in vitro and in vivo recovery of gatifloxacin using microdialysis. The validation parameters of linearity, precision, accuracy and limit of detection were studied as well as stability. Correlation coefficient (r2) obtained was > 0.999 for all calibration curves (20-600 ng.mL-1). Intra- and inter-day precision, expressed as the relative standard deviation (RSD) were less than 1.59 % and 1.33 %, respectively. Acceptable accuracy was achieved for all concentrations (99.17-101.35 %). The limit of quantification of the method was 20 ng.mL-1. The method showed the stability of gatifloxacin when submitted to different conditions. The validated method was applied to study calibration of microdialysis probes. The probe recovery was determined by no net flux experiment in vitro and in vivo. The in vitro and in vivo recovery for gatifloxacin was 30.9 ± 2.9 % and 28.9 ± 0.8 %, respectively. No differences were found between the two approaches. The HPLC method offers advantages because it has no extra sample handling steps; it is sensitive and can be used to determine free concentrations of gatifloxacin in tissues.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pullulan as a stabilizer agent of polymeric nanocapsules for drug delivery

Polymeric stabilizers have received attention in the preparation of nanostructured systems due to their ability to enhance formulation stability. Considering this, the objective of this work was to prepare poly(ε-caprolactone) nanocapsules using the pullulan as a polymeric stabilizer. The nanocapsules were prepared using the interfacial deposition method of preformed polymers and they were characterized in terms of pH, average diameter, polydispersity index, zeta potential, beclomethasone dipropionate content, encapsulation efficiency, photostability and drug release profiles. The formulations showed physicochemical characteristics consistent with nanocarriers for drug delivery such as: average diameter lower than 270 nm, polydispersity indexes lower than 0.2, negative zeta potential (-22.7 to -26.3 mV) and encapsulation efficiencies close to 100%. In addition, the nanocapsules were able to delay the beclomethasone dipropionate photodegradation under UVC radiation and by the dialysis bag diffusion technique, the nanocapsules were able to prolong the drug release. Thus, pullulan could be considered an interesting excipient to formulate polymeric nanocapsules

Avaliação do Polimorfismo e Perfil de Dissolução de Formulações de Carbamazepina

A carbamazepina é um fármaco que apresenta baixa solubilidade, estreita janela terapêutica e exibe polimorfismo. A presença de diferentes polimorfos da carbamazepina em medicamentos está relacionada com propriedades de solubilidade de dissolução limitadas, onde apenas a forma polimórfica III deve estar presente em produtos comerciais. O objetivo do estudo foi avaliar a qualidade de produtos referência, genérico, similar e manipulado de carbamazepina na dose de 200 mg, através da identificação da forma polimórfica presente nos produtos empregando a espectroscopia no infravermelho, calorimetria exploratória diferencial e a difração por raio-X, bem como correlacionar os resultados com os perfis de dissolução. A qualidade dos produtos também foi avaliada mediante o teste do peso médio e de conteúdo. Todas as amostras contendo carbamazepina apresentaram a forma III na sua composição. Nenhuma das formulações apresentou perfil de dissolução semelhante ao produto de referência. Observou-se que todos os produtos contendo carbamazepina estavam de acordo com as especificações farmacopeias em relação ao peso médio e seu conteúdo. A eficácia de dissolução variou de 88,71% a 95,34%. O controle constante de polimorfismo é um passo importante para garantir a qualidade dos produtos, uma vez que a carbamazepina pode se converter em diferentes polimorfos. http://dx.doi.org/10.18226/23185279.v4iss3p16

Validation of a high performance liquid chromatographic method for quantitative determination of boldine in fluid extract of boldo

A simple and specific method was validated for quantification of boldine in fluid extract of boldo (Peumus boldus Mol.) using high-performance liquid chromatography. A reversed-phase C18 , Phenomenex® (150 x 4.6 mm, 4 µm) column was employed. The mobile phase consisted of 0.1 % trifluoroacetic acid and acetonitrile (78:22, v/v) at a flow rate of 0.8 mL/min. The column was maintained at 30 °C and the boldine peak detection was performed at a wavelength of 281 nm. The parameters used in the validation process were: linearity, specificity, precision, accuracy, limit of detection, limit of quantification and robustness. The validated method was selective and linear (r≥0.9991) for boldine concentration considering 5.0, 10.0, 15.0, 20.0 and 25.0 micro;g/mL. The recovery ranged from 90.93 % to 96.24 % and the limit of quantification was 2.41 micro;g/mL. The precision determined was reported as RSD (1.73 %). The method can be successfully applied to measure boldine concentrations in Boldo extract and be included in routine analysis of quality control.Colegio de Farmacéuticos de la Provincia de Buenos Aire

PK/PD modeling of daptomycin against MRSA and MRSE and Monte Carlo simulation for bacteremia treatment

Objectives The aim of this study was to investigate the effect of daptomycin against methicillin-resistant staphylococci (MRSA and MRSE) bacteremia using computer modeling. Methods A pharmacokinetic/pharmacodynamic (PK/PD) modeling strategy to explain the data from an in vitro dynamic model employing time-kill curves for MRSA and MRSE was proposed. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed. Monte Carlo simulations were performed using pharmacokinetic parameters and pharmacodynamic data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. Simulations were conducted to assess the reduction in the number of colony-forming units (CFU)/mL for 18 days of treatment with daptomycin at doses of 6, 8, and 10 mg/kg/24 h or 48 h with variations in creatinine clearance ( CLCR): 15–29 mL/ min/1.73 m2, 30–49 mL/min/1.73 m2, 50–100 mL/min/1.73 m2, as well as for defining the probability of reaching the target fAUC/MIC = 80 in the same dose and clearance range. A PK/PD model with saturation in the number of bacteria in vitro, growth delay, and bacterial death, as well as Hill’s factor, was used to describe the data for both MRSA and MRSE. Results Monte Carlo simulations showed that for MRSA there was a reduction > 2 log CFU/mL with doses ≥ 6 mg/kg/day in 75th percentile of the simulated population after 18 days of treatment with daptomycin, whereas for MRSE this reduction was observed in 95th percentile of the population. Conclusions The presented in vitro PK/PD model and associated modeling approach were able to characterize the timekill kinetics of MRSA and MRSE. Our study based on PTAs suggests that doses ≥ 6 mg/kg/day of daptomycin should be used to treat bacteremia caused by MRSA and MRSE in patients with CLCR of 15–29 mL/min/1.73 m2. For patients with CLCR ≥ 50 mL/min/1.73 m2, it would be necessary to employ a dose of 10 mg/kg/day to treat complicated bacteremias