ABSTRACT
Stability studies of the pharmaceutically important compound finasteride were conducted in order to evaluate decomposition of the drug under forced degradation conditions. A simple stability-indicating liquid chromatography method was developed and validated for the evaluation of finasteride and degradation products formed in pharmaceutical preparations and the raw material. Isocratic LC separation was achieved on a C18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile (52:48 v/v), with a flow rate of 1.0 mL min-1. The alkaline degradation kinetics of the drug were also evaluated and could be best described as second-order kinetics under the experimental conditions applied for the tablets and raw material. Based on in silico studies and molecular weight confirmation, a comprehensive degradation pathway for the drug and the identity of its major product could be suggested without complicated isolation or purification processes. Furthermore, a biological safety study was performed to evaluate the effect of the degraded sample in relation to the intact molecule. The results showed that the degraded sample affected the cell proliferation. Therefore, these studies show that special care must be taken during the manipulation, manufacture and storage of this pharmaceutical drug.
Subject(s)
Chromatography, Liquid/methods , Finasteride , Spectrometry, Mass, Electrospray Ionization/methods , Cell Survival/drug effects , Cells, Cultured , Computer Simulation , Drug Stability , Finasteride/analysis , Finasteride/chemistry , Finasteride/toxicity , Humans , Kinetics , Leukocytes, Mononuclear/metabolism , Linear Models , Reproducibility of Results , Toxicity TestsABSTRACT
This study describes the development and evaluation of stability-indicating liquid chromatographic (LC) and UV spectrophotometric methods for the quantification of ciprofibrate (CPF) in tablets and capsules. Isocratic LC separation was achieved on a RP18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 3.0 with triethylamine (10% v/v) and acetonitrile (35:65 v/v), with a flow rate of 1.0 mL min-1. Detection was achieved with a photodiode array detector at 233 nm. For the spectrophotometric analysis, ethanol and water were used as the solvent and a wavelength of 233 nm was selected for the detection. The methods were validated according to International Conference on Harmonization (ICH) guidelines for validating analytical procedures. Statistical analysis showed no significant difference between the results obtained by the two methods. The proposed methods were successfully applied to the CPF quality-control analysis of tablets and capsules.
Este estudo descreve o desenvolvimento e avaliação de método indicativo da estabilidade por cromatografia líquida (LC) e método por espectrofotometria UV para quantificação de ciprofibrato (CPF) em comprimidos e cápsulas. No método por cromatografia líquida as análises foram realizadas isocraticamente em coluna de fase reversa C18, utilizando fase móvel composta por ácido o-fosfórico (0.1% v/v) pH 3.0, ajustado com trietilamina (10% v/v), e acetonitrila (35:65 v/v), com fluxo de 1,0 mL min-1. A detecção foi realizada em detector de arranjo de diodos a 233 nm. Na análise espectrofotométrica, etanol e água foram utilizados como solventes e o comprimento de onda de 233 nm foi selecionado para a detecção do fármaco. Os métodos foram validados de acordo com as diretrizes do International Conference on Harmonization (ICH). A análise estatística não mostrou diferença significativa entre os resultados obtidos pelos dois métodos. Os métodos foram aplicados com sucesso para análises de controle de qualidade do ciprofibrato em comprimidos e cápsulas.
