TY - JOUR
T1 - 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
AU - Pao, Li Heng
AU - Hsiong, Cheng Huei
AU - Hu, O. Y P
AU - Ho, Shung T.
PY - 2000/9/15
Y1 - 2000/9/15
N2 - For the determination of nalbuphine and its long acting prodrug, sebacoyl dinalbuphine ester (SDN), in biological samples, a reversed-phase high-performance liquid chromatographic method using dual detectors was established. Ultraviolet and fluorescence detectors were connected in series for determining SDN and nalbuphine, respectively. The two analytes and internal standard 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 2500 ng/ml for SDN. The within- and between-day precision and accuracy were all within 10% for both nalbuphine and SDN over these concentrations. The method 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 74.7 min. Formation of nalbuphine after intravenous administration of SDN was observed in the first time point sample (5 min). These results indicate that SDN is rapidly metabolized to its active moiety, nalbuphine, in dogs and no other metabolites are detected in plasma. Copyright (C) 2000 Elsevier Science B.V.
AB - For the determination of nalbuphine and its long acting prodrug, sebacoyl dinalbuphine ester (SDN), in biological samples, a reversed-phase high-performance liquid chromatographic method using dual detectors was established. Ultraviolet and fluorescence detectors were connected in series for determining SDN and nalbuphine, respectively. The two analytes and internal standard 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 2500 ng/ml for SDN. The within- and between-day precision and accuracy were all within 10% for both nalbuphine and SDN over these concentrations. The method 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 74.7 min. Formation of nalbuphine after intravenous administration of SDN was observed in the first time point sample (5 min). These results indicate that SDN is rapidly metabolized to its active moiety, nalbuphine, in dogs and no other metabolites are detected in plasma. Copyright (C) 2000 Elsevier Science B.V.
KW - Nalbuphine
KW - Sebacoyl dinalbuphine ester
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U2 - 10.1016/S0378-4347(00)00326-1
DO - 10.1016/S0378-4347(00)00326-1
M3 - Article
C2 - 11076077
AN - SCOPUS:0034666474
SN - 1387-2273
VL - 746
SP - 241
EP - 247
JO - Journal of Chromatography B: Biomedical Sciences and Applications
JF - Journal of Chromatography B: Biomedical Sciences and Applications
IS - 2
ER -