Dissertation > Medicine, health > Pharmacy > Pharmacology

Pharmacokinetics of Progesterone Cream in Beagle Dogs Determined with LC-MS/MS

Author GuLiNuEr·TaXiTieMuEr
Tutor GaoXiaoLi
School Xinjiang Medical University
Course Pharmacy
Keywords progesterone liquid chromatography-tandem mass spectrometry (LC- MS/ MS) plasma drug concentration pharmacokinetics
Type Master's thesis
Year 2011
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Objective: To establish a Ultra liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative of progesterone in Beagle plasma. To study the pharmacokinetics and bioavailability of the progesterone cream and capsule in Beagle dogs. Method: Chromatographic separation was performed on a C18 column (150mm×4. 6mm, 5μm) with methanol-0.1% formic acid solution (90:10) as the mobile phase. A trip-quadrupole tandem mass spectrum with the atmospheric pressure chemical ionization (APCI) source was applied and positive ion multiple reaction monitoring mode (MRM) was operated. Six Beagle dogs were randomly devided into two groups. They received single dose of progesterone cream (test formulation) 59.26mg/kg or progesterone capsule (reference formulation) 5.3mg/kg. Plasma samples were collected at designed time. Plasma concentration of progesterone was determined by LC-MS/MS and pharmacokinetic parameters were calculated. Results: 1) The linear range of progesterone was 0.4~50ng/ml, by the UPLC-MS/MS, Within day RSD and day to day RSD were both less than7.5%. The method recovery and extraction recovery of the assay were 94. 4%~99. 7% and 81. 2%~92. 4% respectively. The detection limit was 0. 2ng/ml. 2) Evaluated the pharmacokinetic parameters using by UPLC-MS/MS, and Cmax for the progesterone cream (test formulation) and progesterone capsule (reference formulation) were 19.55±6.52ng/ml and 19. 84±9.89 ng/ml, respectively, Tmax were18.67±9.35h and 1.33±0.52h, MRT (0-∞) were 47. 53±27. 12h and 40. 04±27. 22h, AUC (0-∞) for both formulation were 534.99±179.10 ng·h/ml and 339.00±175.79 ng·h/ml, respectively. Relative bioavailability of progesterone cream was 14.71±4.23%. Conclusion: 1) The established method of LC-MS/MS determining the concentration of progesterone in plasma has the characteristic of strong specificity, high sensitivity and good accuracy. 2) Pharmacokinetic parameters shows that after transdermal administration of progesterone, had achieved effective plasma concentration. The plasma concentration in the dog was released and maintain stable, and maintained permanent physiological effect, had delayed release effect. 3) The bioavailability of transdermal administration was achieved 14.71%. But compared with the progesterone capsule, the pharmacokinetic parameters of the progesterone cream presented significant slowing releasing character.

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