Quantitative analysis of R-84760, a selective kappa-opioid receptor agonist, in plasma by liquid chromatography with electrospray ionization tandem mass spectrometry.
A sensitive method for monitoring R-84760, a selective kappa-opioid receptor agonist, in plasma using liquid chromatography with electrospray ionization tandem mass spectrometry was explored. R-84760 and internal standard (I.S., d8-R-84760) were extracted from human or various animal plasmas with ethyl acetate. The analysis was performed by the selected reaction monitoring method, and the precursor-product combinations of m/z 399-328 for R-84760 and m/z 407-328 for I.S. were chosen for quantification. The calibration curve was linear in the range 5-500 pg/ml, and the limit of quantification was 5 pg/ml using 1 ml of human plasma. Pharmacokinetic studies of R-84760 in rats, dogs, and monkeys were performed by this method. The plasma concentration of unchanged form after administration at a trace dosage amount was able to be monitored. Interspecies correlations of pharmacokinetic parameters obtained in animals were utilized to estimate pharmacokinetic behavior in humans. The results showed that it is possible to perform pharmacokinetic studies on R-84760 by this quantitative analysis.
Kobayashi
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N
Analytical and Metabolic Research Laboratories, Sankyo Company, Tokyo, Japan. nobuhi@shina.sankyo.co.jp
Naganuma
H
H
D000700:Analgesics / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D011759:Pyrrolidines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012015:Reference Standards; D015203:Reproducibility of Results; D013843:Thiazines / Q000097:blood* / Q000493:pharmacokinetics
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013843:Thiazines; C091101:R 84760