A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate

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    Abstract

    © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.Background: Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother-baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 L of plasma, and with application to human breast milk. Methods: Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water-methanol-acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection. Results: Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration-time curve for the interval 0-12 hours was 10,726 mcg·h·L -1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration. Conclusions: An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.
    Original languageEnglish
    Pages (from-to)493-498
    JournalTherapeutic Drug Monitoring
    Volume38
    Issue number4
    DOIs
    Publication statusPublished - 2016

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    Human Milk
    Tandem Mass Spectrometry
    Liquid Chromatography
    Breast
    Pharmaceutical Preparations
    Psychotropic Drugs
    sultopride
    Plasma Volume
    Drug Monitoring
    Lactation
    Psychotic Disorders
    Antipsychotic Agents
    Methanol
    Milk
    Mothers
    Pregnancy
    Water
    Health

    Cite this

    @article{7b9018f41f88499184b6045837c3c0b3,
    title = "A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate",
    abstract = "{\circledC} Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.Background: Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother-baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 L of plasma, and with application to human breast milk. Methods: Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water-methanol-acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection. Results: Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration-time curve for the interval 0-12 hours was 10,726 mcg·h·L -1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5{\%} of the maternal plasma concentration. Conclusions: An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.",
    author = "Sean O'Halloran and A. Wong and David Joyce",
    year = "2016",
    doi = "10.1097/FTD.0000000000000300",
    language = "English",
    volume = "38",
    pages = "493--498",
    journal = "Therapeutic Drug Monitoring",
    issn = "0163-4356",
    publisher = "Lippincott Williams & Wilkins",
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    T1 - A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate

    AU - O'Halloran, Sean

    AU - Wong, A.

    AU - Joyce, David

    PY - 2016

    Y1 - 2016

    N2 - © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.Background: Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother-baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 L of plasma, and with application to human breast milk. Methods: Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water-methanol-acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection. Results: Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration-time curve for the interval 0-12 hours was 10,726 mcg·h·L -1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration. Conclusions: An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.

    AB - © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.Background: Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother-baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 L of plasma, and with application to human breast milk. Methods: Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water-methanol-acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection. Results: Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration-time curve for the interval 0-12 hours was 10,726 mcg·h·L -1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration. Conclusions: An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.

    U2 - 10.1097/FTD.0000000000000300

    DO - 10.1097/FTD.0000000000000300

    M3 - Article

    VL - 38

    SP - 493

    EP - 498

    JO - Therapeutic Drug Monitoring

    JF - Therapeutic Drug Monitoring

    SN - 0163-4356

    IS - 4

    ER -