Determination of 8-methoxypsoralen in mouse plasma by high performance liquid chromatography and its application to pharmacokinetic study / 北京大学学报(医学版)

OBJECTIVE@#To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP.@*METHODS@#8-MOP was separated on a Waters Symmetry18 column (250 mm × 4.6 mm, 5 μm) and determined by HPLC using isocratic elution, and 5-methoxypsoralen was used as internal standard. The mobile phase consisted of methanol-water (55:45, V/V) at a flow rate of 1.0 mL/min. The excitation and emission wavelength of fluorescence detector were set at 334 nm and 484 nm respectively, and the internal standard method was used for quantitative analysis. In the study, 60 healthy ICR male mice were randomly divided into twelve groups. The mice in control group were administered intragastrically with 1% Tween 80, and the mice in the other eleven groups were administered intragastrically with 8-MOP (40 mg/kg). Plasma concentrations of 8-MOP in the mice at different time points after treatment were determined by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software.@*RESULTS@#The calibration curve of 8-MOP was linear with a correlation coefficient of 0.999 3 over the concentration range of 0.05 to 10 mg/L, and the limit of detection was 0.015 mg/L. The average recoveries of 8? MOP at three different concentrations (0.10, 0.50, 2.5 mg/L) were from 92.5% to 100.6%. The intra-day precision of 8-MOP was from 3.3% to 8.2%, while the inter-day precision was from 3.4% to 6.7% at three spiked concentration levels. The extraction recoveries of 8-MOP were from 90.9% to 92.0%, and the plasma samples could be stored at -80°C for 15 days at least at three spiked concentration levels. 8-MOP could be detected in mouse plasma 5 min after intragastrical administration to the mice (1.4 mg/L). The concentration of 8-MOP in the mouse plasma reached a maximum 2 h after administration, and 8-MOP could still be detected 24 h after administration (1.1 mg/L). t1/2 was (39.21±3.65) h, Cmax was (2.31±0.02) mg/L, tmax was (2.00±0.00) h, and AUC0-t was (33.34±1.19) (h×mg)/L.@*CONCLUSION@#The proposed method is accurate and simple,suitable for pharmacokinetics of 8-MOP in mice.

study of pentobarbitone-methoxsalen interaction in rats

Experiments carried out to study pentobarbitonemethoxsalen interaction in rats. The study was conducted on adult albino rats [150-250 g, either sex] in two phases. In phase I, methoxsalen was administered [5, 10 and 15 mg/kg i.p. x 5 days] and pentobarbitone was administered [30 mg/kg i.p.] 24 hours after the last dose of methoxsalen. In phase II, methoxsalen was administered [10 mg/kg p.o. x two weeks] and pentobarbitone was administered [in dose of 15, 20 and 30 mg/kg i.p.] 24 hrs after the last dose of methoxsalen, CNS activity such as pinna, sound and righting reflex were observed. In phase I, pentobarbitone caused CNS depression in methoxsalen treated and control groups. In phase II, pentobarbitone in dose of 15, 20 and 30 mg/kg in methoxsalen treated rats also caused CNS depression in dose dependent manner. The action of pentobarbitone was potentiated in methoxsalen treated rats hence barbiturates whenever indicated in patients on methoxsalen, should be used with caution

Laboratory and clinical evaluation of a new formulation of 8-methoxypsoralen in the treatment of vitiligo

A new formulation of 8-methoxypsoralen [8-MOP] capsule was investigated both in the laboratory and clinically. Laboratory investigations showed that the new formulation is absorbed better than the currently available 8-MOP and it reaches a peak blood level in 45 minutes. Clinically, 14 vitiligo patients received the new drug in a dose ranging from 0.25-0.4 mg/kg body weight and exposed their vitiliginous patches to the sun at midday [45 minutes after drug ingestion]. An excellent response [>75% of a test patch repigmented] was obtained in 5 patients [35.7%], a good response [50-75% of the patch covered] was obtained in 3 patients [21.4%] and an unsatisfactory response [<50% of the patch covered] was obtained in 6 patients [42.9%]. Side effects were very minimal. The new formulation of 8-MOP capsule is safe, more effects than the marketed tablet formulation and its dose can be raised in nonresponding cases without producing nausea or vomiting