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

Li Heng Pao, Cheng Huei Hsiong, O. Y P Hu, Shung T. Ho

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19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume746
Issue number2
DOIs
Publication statusPublished - Sep 15 2000
Externally publishedYes

Fingerprint

Nalbuphine
Pharmacokinetics
Prodrugs
Plasmas
Liquids
Detectors
sebacoyl dinalbuphine ester
Metabolites
Fluorescence
Calibration

Keywords

  • Nalbuphine
  • Sebacoyl dinalbuphine ester

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

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title = "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",
abstract = "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.",
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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

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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.

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