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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
Author(s) -
Huang PeiWei,
Liu HungTa,
Hsiong ChengHuei,
Pao LiHeng,
Lu ChihCherng,
Ho ShungTai,
Hu Oliver YoaPu
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2867
Subject(s) - chemistry , chromatography , nalbuphine , liquid chromatography–mass spectrometry , high performance liquid chromatography , formic acid , mass spectrometry , ammonium formate , tandem mass spectrometry , electrospray ionization , detection limit , ammonium acetate , selected reaction monitoring , biochemistry , receptor , opioid
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 × 100 mm, 1.7 µm). The mobile phase was composed of acetonitrile and water (83:17, v/v) that contained 0.2% formic acid and 4 m m ammonium formate at a flow rate of 0.25 mL/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 20 ng/mL, with correlation coefficients ≥0.995. The lower limit of quantification was set at 0.05 ng/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. Copyright © 2013 John Wiley & Sons, Ltd.