{
    "abstract": "Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. To prevent PPH, the WHO recommends administration of oxytocin (OT) immediately after birth, i.e. during the third stage of labour (TSL). Previous studies demonstrate that methods to quantify OT in biological matrices, e.g. enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) lack the specificity and/or sensitivity to accurately quantify OT in plasma from women administered OT during TSL. This is due to increased metabolic clearance of OT in late-stage pregnancy and at the time of childbirth, resulting in extremely low OT plasma concentrations. This study describes the development of an ultra-sensitive bioanalytical method that overcomes the issues previously reported and enables accurate pharmacokinetic analyses of exogenously administered OT in TSL.\nA selective and sensitive assay to quantify OT in TSL plasma was developed. Immunoprecipitation (IP) was applied to selectively extract OT from the TSL plasma, thereby generating clean extracts compatible with nanoflow LC (nLC). nLC-MS/MS was chosen for its high sensitivity and ability to differentiate between OT and potentially co-captured OT-like immunoreactive products.\nThe presented methodology is accurate and precise, with a good linear fit between 100-10\u2009000\u2009fg\u2009mL\nThe presented IP-nLC-MS/MS method succeeded in overcoming the sensitivity challenge related to the assay of OT in TSL plasma and thereby revealing the PK profiles of OT in TSL plasma clinical study samples.",
    "authors": [
        {
            "affiliation": "Janssen Pharmaceutica, Bioanalytical Discovery & Development Sciences, Beerse, Belgium.",
            "firstname": "Sebastiaan",
            "initials": "S",
            "lastname": "Bijttebier"
        },
        {
            "affiliation": "Drug Delivery Disposition and Dynamics, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.",
            "firstname": "Tri-Hung",
            "initials": "TH",
            "lastname": "Nguyen"
        },
        {
            "affiliation": "Drug Delivery Disposition and Dynamics, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.",
            "firstname": "Michelle P",
            "initials": "MP",
            "lastname": "McIntosh"
        },
        {
            "affiliation": "Drug Delivery Disposition and Dynamics, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.",
            "firstname": "Carl",
            "initials": "C",
            "lastname": "Kirkpatrick"
        },
        {
            "affiliation": "Janssen Pharmaceutica, Clinical Pharmacology, Beerse, Belgium.",
            "firstname": "Bart",
            "initials": "B",
            "lastname": "Remmerie"
        },
        {
            "affiliation": "Janssen Pharmaceutica, Bioanalytical Discovery & Development Sciences, Beerse, Belgium.",
            "firstname": "Lieve",
            "initials": "L",
            "lastname": "Dillen"
        },
        {
            "affiliation": "Drug Delivery Disposition and Dynamics, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.",
            "firstname": "Pete",
            "initials": "P",
            "lastname": "Lambert"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",
    "doi": "10.1111/bcp.16135",
    "journal": "British journal of clinical pharmacology",
    "keywords": [
        "immunoprecipitation",
        "liquid chromatography\u2013tandem mass spectrometry",
        "oxytocin",
        "pharmacokinetic profiles",
        "third stage of labour"
    ],
    "methods": null,
    "publication_date": "2024-06-19",
    "pubmed_id": "38890002",
    "results": "The presented methodology is accurate and precise, with a good linear fit between 100-10\u2009000\u2009fg\u2009mL",
    "title": "Application of immunocapture and nanoflow LC-MS/MS to overcome the barriers to the quantitation of oxytocin in plasma of women in third stage labour.",
    "xml": "<Element 'PubmedArticle' at 0x788505c93a10>"
}