Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV agent, by high-performance liquid chromatography in plasma from rat, dog and human.
A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).
Xu
Z Q
ZQ
MediChem Research, Inc., and Sarawak MediChem Pharmaceuticals, Inc., Lemont, IL 60439, USA. zxu@mcr.medichem.com
Norris
K J
KJ
Weinberg
D S
DS
Kardatzke
J
J
Wertz
P
P
Frank
P
P
Flavin
M T
MT
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015331:Cohort Studies; D003374:Coumarins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D039681:Pyranocoumarins; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D019380:Anti-HIV Agents; D003374:Coumarins; D039681:Pyranocoumarins; C075959:calanolide A