Validated analytical study of the effect of Lycopene on the pharmacokinetics of Paracetamol and Chlorzoxazone in rats

Lycopene was reported to influence some cytochrome P450 enzymes activity. The present study investigates the effect of lycopene on the pharmacokinetics of paracetamol and chlorzoxazone. Lycopene (20 mg/kg) was intra-peritoneally administered to two groups of rats for eight consecutive days and two other groups were given vehicle. On the eighth day, chlorzoxazone and paracetamol were separately intravenously administered to a lycopene group and a control group. Blood samples were collected at different time intervals, treated and analyzed using HPLC. The HPLC method used for paracetamol analysis was based on isocratic elution using a mobile phase consisting of water: methanol, (77:23 v/v) at a flow rate 1 mL min−1, Kromasil C18 column, and UV detection at 254 nm using caffeine as internal standard. About chlorzoxazone, separation was carried out using water: acetonitrile (60: 40, v/v) as the mobile phase at a flow rate 1 mL min−1, Inertsil ODS-3 C18 column, UV detection at 283 nm and esomeprazole as internal standard. Statistical analysis of the pharmacokinetic data using student t test showed a significant increase in AUC 0-t , AUC 0-Inf and t1/2 of paracetamol (P<0.05) and of chlorzoxazone (P<0.05) in the groups pretreated with lycopene (20 mg/kg), significant increase in the volume of distribution of paracetamol (P < 0.05), but no significant difference in that of chlorzoxazone. In other words, paracetamol and chlorzoxazone showed significant decrease (P < 0.05), respectively. These results demonstrate that treatment of rats with Lycopene (20mg/kg, ip) has a significant effect on the metabolic clearance and the pharmacokinetics of both drugs

Simultaneous determination of ciprofloxacin hydrochloride and metronidazole in spiked human plasma by ultra performance liquid chromatography-tandem mass spectroscopy.

Ciprofloxacin HCl (CIP) and Metronidazole (MET) are antibacterial drugs used in combination for treatment of mixed aerobic/anaerobic infections. An UPLC-MS/MS method was developed for the simultaneous estimation of CIP and MET in spiked human plasma using sildenafil citrate as an internal standard (IS). Protein precipitation was used for analyte extraction. The chromatographic separation was completed within 6 min using a mobile phase of 0.1% formic acid in water and acetonitrile (70: 30, v/v), Zorbax C18, 100 x 4.6 mm, 3.5 μm analytical column, at a flow rate of 0.5 mL min-1. Multiple reaction monitoring (MRM) transitions were measured in the positive ion mode. Validation of the method showed standard curves to be linear in the range of 10-4000 ng mL-1 for CIP and 30-12000 ng mL-1 for MET with mean correlation coefficient exceeding 0.999. In human plasma, CIP and MET were stable for at least 36 days at –70 ± 5 °C, 6 hours at ambient temperature and after three freeze thaw cycles. After extraction from plasma, the samples were stable in auto sampler at 22 °C for 6 hours. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies.