Determination of morphine by high-performance liquid chromatography with electrochemical detection

Application to human and rabbit pharmacokinetic studies

Wen Jinn Liaw, Shung Tai Ho, Jhi Joung Wang, Oliver Yoa Pu Hu, Jih Heng Li

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

A rapid, sensitive, precise and accurate high-performance liquid chromatographic assay with coulometric electrochemical detection was developed for the determination of morphine in human, rabbit, pig and dog plasma. It includes a one-step extraction procedure with hexane-isoamyl alcohol (1:1, v/v) at pH 8.9 (adjusted with phosphoric acid) and reversed-phase liquid chromatography on a μPorasil column. The mobile phase was composed of 5 mM sodium acetate buffer (pH 3.75)-acetonitrile (25:75, v/v). A flow-rate of 1.2 ml/min at 20°C was used. The working potentials for the electrochemical detector were +0.20 V for detector cell 1, +0.55 V for detector cell 2 and +0.75 V for the guard cell. The limit of detection of morphine was 100 pg/ml of plasma. Repeatability, precision and accuracy were also determined concomitantly. The calibration graphs were linear in the concentration range 0.25-250 ng/ml with correlation coefficients of 0.998±0.01 and with a minimum intercept of 0.05±0.08. The precision in plasma was acceptable, with coefficients of variation less than 11%. The absolute recoveries of morphine and nalbuphine (internal standard) were between 86 and 89% and independent of morphine concentration. Pharmacokinetics after oral morphine [MST Continus(TM) (morphine sulphate tablets) 30 mg, Bard Pharmaceutical, Cambridge, UK] in humans revealed a one-compartment first-order absorption model with one absorption phase and one elimination phase. The absorption and elimination half-lives were 2.46 and 1.80 h, respectively. Pharmacokinetics after intravenous morphine (3 mg/kg) in rabbits showed a linear two-compartment open model with one distribution phase and one elimination phase. The distribution and elimination half-lives were 0.5 and 33.8 h, respectively. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalJournal of Chromatography B: Biomedical Applications
Volume714
Issue number2
DOIs
Publication statusPublished - Sep 4 1998
Externally publishedYes

Fingerprint

Pharmacokinetics
High performance liquid chromatography
Morphine
Detectors
Plasmas
Nalbuphine
Sodium Acetate
Liquid chromatography
Hexanes
Tablets
Assays
Buffers
Flow rate
Calibration
Recovery
Liquids
Pharmaceutical Preparations

Keywords

  • Morphine

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Determination of morphine by high-performance liquid chromatography with electrochemical detection : Application to human and rabbit pharmacokinetic studies. / Liaw, Wen Jinn; Ho, Shung Tai; Wang, Jhi Joung; Hu, Oliver Yoa Pu; Li, Jih Heng.

In: Journal of Chromatography B: Biomedical Applications, Vol. 714, No. 2, 04.09.1998, p. 237-245.

Research output: Contribution to journalArticle

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