Pharmacokinetics study of the anti-HIV lead compound DAAN-5508 in rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop and validate a LC-MS/MS method for quantitative analysis of the new anti-HIV candidate DAAN-5508 in rat plasma, and to study its pharmacokinetics and bioavailability in rats. METHODS: The plasma samples were treated with methanol for precipitating proteins. The chromatographic separation was performed with a gradient elution using 0.1% formic acid solution and methanol containing 0.1% formic acid. The flow rate was 0.3 mL · min-1. The MS detection was conducted using an LC-MS/MS in positive ion electrospray and multiple reactions monitoring (MRM) mode. RESULTS: Good linearity was obtained over the concentration range of 0.2-2500 ng · mL-1 for DAAN-5508 (r2=0.9998), with the lower limit of quantification at 0.2 ng · mL-1. The recovery of DAAN-5508 was greater than 80%. The precision and the accuracy met the requirements for bioanalysis. The method was applied for pharmacokinetics study of DAAN-5508 in rats. After a single iv(5 mg · kg-1) or oral dose (15 mg · kg-1) of DAAN-5508 to rats, the plasma concentration of DAAN-5508 showed a biphasic decline. The elimination half-lives were 2.6 and 4.6 h for intravenous and oral administration, respectively. The absorption of DAAN-5508 was rapid after oral administration. The peak level (188.0 ± 62.33) ng · mL-1 was reached at 1 h. The oral bioavailability was 12%. CONCLUSION: The developed the LC-MS/MS method is selective, sensitive, rapid and simple. It is suitable for the in vivo pharmacokinetics study of DAAN-5508 in rats.