Simultaneous determination of nalbuphine and its prodrug sebacoly dinalbuphine ester in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in humans

Pei Wei Huang, Hung Ta Liu, Cheng Huei Hsiong, Li Heng Pao, Chih Cherng Lu, Shung Tai Ho, Oliver Yoa Pu Hu

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6 Citations (Scopus)

Abstract

A rapid, simple, sensitive and selective ultraperformance liquid chromatography-tandem spectrometry (UPLC-MS/MS) method for the determination of nalbuphine and its prodrug sebacoly dinalbuphine ester (SDE) was developed and validated in human plasma. The sample pretreatment involves basification and iterative liquid-liquid extraction with ethyl-ether-dichloromethane (7:3, v/v) solution, followed by LC separation and positive electrospray ionization (ESI) API-3000 mass spectrometry detection. The chromatography was on a Waters Acquity UPLC BEH HILIC column (2.1×100mm, 1.7μm). The mobile phase was composed of acetonitrile and water (83:17, v/v) that contained 0.2% formic acid and 4mm ammonium formate at a flow rate of 0.25mL/min. Ethylmorphine and naloxine were selected as the SDE and nalbuphine internal standard (IS), respectively. The calibration curve for both was linear over the range from 0.05 to 20ng/mL, with correlation coefficients ≥0.995. The lower limit of quantification was set at 0.05ng/mL. The intra- and inter-day precision values for nalbuphine and SDE were acceptable as per FDA guidelines. The method was applied successfully to determine nalbuphine concentration in human plasma samples obtained from four Taiwanese volunteers receiving intramuscularly administration of sebacoyl dinalbuphine ester. The method is sensitive, selective and directly applicable to human pharmacokinetic studies involving nalbuphine.

Original languageEnglish
Pages (from-to)831-837
Number of pages7
JournalBiomedical Chromatography
Volume27
Issue number7
DOIs
Publication statusPublished - Jul 1 2013
Externally publishedYes

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Keywords

  • Nalbuphine
  • Sebacoyl dinalbuphine ester (SDE)
  • UPLC-MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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