Prodrug behaviour of nicotinoylmorphine esters

Broekkamp, C.L.E.; Oosterloo, S. K.; Rijk, H.

doi:10.1111/j.2042-7158.1988.tb06310.x

Cited by 11 publications

(2 citation statements)

References 9 publications

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“…Previous studies of the ester prodrug indicate that the safety profile and pharmacological actions are similar to the parent compound (Broekkamp et al ., ; Hemstrom et al ., ; He et al ., ). With the advantage of prolonged duration (from a few days to a few weeks), SDE is currently in phase III study to prove its efficacy and safety on post‐operation patients.…”

Section: Introductionmentioning

confidence: 98%

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

Huang

Liu

Hsiong

et al. 2013

Biomedical Chromatography

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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 mm 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.

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Section: Introductionmentioning

confidence: 98%

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

Huang

Liu

Hsiong

et al. 2013

Biomedical Chromatography

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“…[7][8][9][10][11][12] In the present study, the morphine 3-esters, when compared with the parent compound, were up to 4600-, 300-, and 9300-fold less potent for binding to µ-, δ-, and κ-opioid receptors, respectively ( Table 4). [7][8][9][10][11][12] In the present study, the morphine 3-esters, when compared with the parent compound, were up to 4600-, 300-, and 9300-fold less potent for binding to µ-, δ-, and κ-opioid receptors, respectively ( Table 4).…”

Section: Resultsmentioning

confidence: 51%

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Mignat

Heber

Schlicht

et al. 1996

Journal of Pharmaceutical Sciences

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With the intention of preparing prodrugs, 10 morphine 3-esters were synthesized and evaluated in vitro for opioid receptor binding and enzymatic hydrolysis. The results of binding assays performed on homogenates of guinea pig brain demonstrate a loss in affinity of morphine to mu-, delta-, and kappa-receptors by esterification at the 3-position. The conversion of the esters to morphine was determined in human plasma by HPLC analysis. The half-lives of hydrolysis ranged from 0.5 to > 300 h. The investigations indicate that esterification at the 3-position results in morphine prodrugs with variable hydrolytic stability. Sterically hindered morphine 3-esters may be a promising approach to manipulate the rate of release of morphine.

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Determination of morphine 3-esters in rabbit plasma by high-performance liquid chromatography with ultraviolet detection

Otter

Mignat

Heber

et al. 2000

Biomed. Chromatogr.

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A sensitive high-performance liquid chromatographic (HPLC) method for the quantitation of the morphine 3-esters 1[3-(2, 2-dimethylvaleroyl)-morphine (A), 3-(2-phenylbenzoyl)-morphine (B) and 3-(2,2-diphenylpropionyl)-morphine (C)] in rabbit plasma is described. Sample preparation was based on reversed-phase solid-phase extraction. The compounds were separated on C(18) reversed-phase analytical columns and then determined by ultraviolet detection. The recovery from plasma was 78.7 +/- 7.4%, 69.1 +/- 6.9% and 75 +/- 7.2% (mean +/- SD) for A, B, and C, respectively. The present method enabled the detection limit of 0.2, 0.2 and 0.1 ng and quantification limit of 20, 10 and 10 ng/ml for A, B and C, respectively. The developed method was used for determination of the plasmakinetics of these morphine 3-esters in rabbits.

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Prodrug behaviour of nicotinoylmorphine esters

Cited by 11 publications

References 9 publications

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

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

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Determination of morphine 3-esters in rabbit plasma by high-performance liquid chromatography with ultraviolet detection

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