High-performance liquid chromatographic method for the simultaneous determination of nalbuphine and its prodrug, sebacoyl dinalbuphine ester, in dog plasma and application to pharmacokinetic studies in dogs
Lh. Pao et al., High-performance liquid chromatographic method for the simultaneous determination of nalbuphine and its prodrug, sebacoyl dinalbuphine ester, in dog plasma and application to pharmacokinetic studies in dogs, J CHROMAT B, 746(2), 2000, pp. 241-247
For the determination of nalbuphine and its long acting prodrug, sebacoyl d
inalbuphine ester (SDN), in biological samples, a reversed-phase high-perfo
rmance liquid chromatographic method using dual detectors was established.
Ultraviolet and fluorescence detectors were connected in series for determi
ning SDN and nalbuphine, respectively. The two analytes and internal standa
rd were extracted from plasma by alkaline liquid-liquid extraction using n-
hexane-isoamyl alcohol (9.1, v/v). The calibration curve for nalbuphine was
linear over the range from 10 to 2500 ng/ml, while the range was 25 to 250
0 ng/ml for SDN. The within- and between-day precision and accuracy were al
l within 10% for both nalbuphine and SDN over these concentrations. The met
hod was applied successfully to a pharmacokinetic study of SDN administered
at 20 mg/kg to two beagle dogs. Pharmacokinetic analysis revealed that SDN
followed a linear one-compartment model with an elimination half-life of 7
4.7 min. Formation of nalbuphine after intravenous administration of SDN wa
s observed in the first time point sample (5 min). These results indicate t
hat SDN is rapidly metabolized to its active moiety, nalbuphine, in dogs an
d no other metabolites are detected in plasma. (C) 2000 Elsevier Science B.
V. All rights reserved.