Assessment by HPLC of the degradation behavior of acitretin under hydrolytic, oxidative, photolytic and thermal stress conditions

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation. The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies. Therefore, an isocratic RP-HPLC-UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products. Efficient chromatographic separation was achieved on a Thermo beta-basic column C18 (100 mm×4.6 mm, 5 μm) with mobile phase containing 0.3% (v/v) glacial acetic acid with acetonitrile (ACN) and isopropyl alcohol (IPA) in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm. The method was validated for specificity, linearity, precision, accuracy and robustness. The calibration plot was linear over the concentration range of 50-150 μg/mL with a correlation coefficient (r (2)) of 0.999. The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions. The degradation rate constant (K), half-life (t 1/2), and t 90 were calculated. Degradation of acitretin followed pseudo-first-order kinetics. The drug was found to be less stable under acidic and photolytic degradation conditions: the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698% and 0.0008402% min(-1), respectively. The LOD for acitretin and the known impurities were at a level below 0.02%. The method shows consistent recoveries for ACTR (99.8%-101.2%) and also for its known impurities (97.2-101.3%). The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and useful for characterizing the stability of this chemical.

Central nervous system activity of Illicium verum fruit extracts

OBJECTIVE@#To research the acute toxicity of Illicium verum (I. verum) fruit extracts and its action on central nervous system.@*METHODS@#The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I. verum. Male albino rats and mice were utilized for study. The powdered material was successively extracted with n-hexane, ethyl acetate and methanol using a Soxhlet extractor. Acute toxicity studies were performed as per OECD guidelines. The CNS activity was evaluated on parameters of general behavior, sleeping pattern, locomotor activity, anxiety and myocoordination activity. The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each. The drug was administered by intraperitoneal route according to body weight. The dosing was done as prescribed in each protocol.@*RESULTS@#Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time, produced alteration in general behavior pattern, reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity. The three extracts of I. verum at the dose of 200 mg, methanol extract was found to produce more prominent effects, then hexane and ethylacetate extracts.@*CONCLUSIONS@#The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.

Influence of Withania somnifera on obsessive compulsive disorder in mice

OBJECTIVE@#To study the influence of methanolic and aqueous extract of Withania somnifera (W. somnifera) root on the marble-burying behavior of mice a well-accepted model of obsessive compulsive behavior.@*METHODS@#Mice were divided in different groups (n = 6). Fluoxetine (5, 10, 15 mg/kg), (10, 25, 50, 100 mg/kg) and methanolic extract W. somnifera (MEWS) (10, 25, 50, 100 mg/kg) were administered i.p. 30 min. prior to the assessment of marble burying behavior and locomotor activity. The control group received vehicle of the extract.@*RESULTS@#Administration of aqueous extracts W. somnifera (AEWS) and MEWS (50 mg/kg) successively decreased the marble burying behavior activity without affecting motor activity. This effect of AEWS and MEWS was comparable to standard fluoxetine, ritanserin and parachlorophenylalanine.@*CONCLUSIONS@#W. somnifera extract is effective in treating obsessive compulsive disorder.