Simultaneous Determination of Plasma Betamethasone Disodium Phosphate and Betamethasone in Rabbit by High Performance Liquid Chromatography
WEN-SHENG CHENG1, JIIN-LONG CHEN2 AND CHIAO-HSI CHIANG2*
1. Department of Clinical Pharmacy, National Army Beitou Hospital, 60 Sinmin Road, Beitou District, Taipei, Taiwan, R.O.C.
2. School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Sec. 6, Taipei, Taiwan, R.O.C.
(Received: April 3, 2008 ; Accepted: August 10, 2009)
ABSTRACT
Betamethasone disodium phosphate (BDP), a hydrophilic prodrug of betamethasone (BTM), was rapidly converted into betamethasone in blood following intravenous administration. In this study, we established an analytical method of high performance liquid chromatography (HPLC) to simultaneously determine BDP and its free base BTM in plasma samples. The calibration curves demonstrate good linearity (BDP, R2 = 0.99999; BTM, R2 = 0.99997) and reproducibility within a range from 50 ng/mL to 6000 ng/mL. The analytical method was applied to determine the pharmacokinetics of BTM and BDP following intravenous bolus injection of BDP in New Zealand white rabbits (0.4 mg/kg). The determined pharmacokinetic parameters were listed as follows: for BDP, half-life: 13.69 ± 2.70 min (Mean ± SEM, n = 6), clearance: 3.96 ± 0.45 mL/min/kg and distribution volume: 72.9 ± 9.67 mL/kg; for BTM, half-life: 228.58 ± 72.9 min, clearance: 3.50 ± 1.18 mL/min/kg, and distribution volume: 327.57 ± 69.9 mL/kg. The established HPLC analytical method and related pharmacokinetic parameters of BDP and BTM might be potentially applied to use these drug administration in the treatment of respiratory relevant diseases.
Key words: betamethasone disodium phosphate (BDP), betamethasone (BTM), high performance liquid chromatography (HPLC)