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Research Article

Determination of caffeine, paraxanthine, theophylline and theobromine in premature infants by HILIC-MS/MS

    Shi-Yu Wen‡

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    ‡Authors contributed equally to this work as co-first authors.

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    ,
    Hong Ma‡

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China

    The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, 210031, China

    ‡Authors contributed equally to this work as co-first authors.

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    ,
    Xiang-Long Chen

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

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    ,
    Yang Zhao

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China

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    ,
    Yan Liu

    Jiangsu Health Development Research Center, Nanjing, 210036, China

    China National Health & Family Planning Commission Contraceptives Adverse Reaction Surveillance Center, Nanjing, 210036, China

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    ,
    Yue Li

    Department of Pediatrics, Jiangsu Women & Children Health Hospital, Nanjing, 210036, China

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    ,
    Chao Lu

    Department of Pediatrics, Jiangsu Women & Children Health Hospital, Nanjing, 210036, China

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    ,
    Yong-Qing Wang

    *Author for correspondence: Tel.: +86 256 8307 601;

    E-mail Address: wyqjsph@163.com

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China

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    &
    Lu-Ning Sun

    **Author for correspondence:

    E-mail Address: sunluning0521@aliyun.com

    Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China

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    Published Online:24 Feb 2023https://doi.org/10.4155/bio-2022-0131

    Abstract

    Aim: Caffeine is a central nervous system stimulant, used to treat apnea of prematurity. A hydrophilic interaction chromatography–tandem mass spectrometry (HILIC-MS/MS) approach was developed to detect caffeine, paraxanthine, theophylline and theobromine in premature infants. Method: Protein precipitation of plasma samples (10 μl) was carried out by treating with acetonitrile containing caffeine-13C3. The separation was carried out on an ACQUITY HPLC® BEH HILIC column. Caffeine and its metabolites were quantified by multiple reaction monitoring modes with positive electrospray ionization. Results: The established method had a good linear relationship in the range of 0.0600–60.0 μg/ml for caffeine, 0.0250–7.50 μg/ml for theobromine and 0.0150–4.50 μg/ml for paraxanthine and theophylline. Conclusion: A HILIC-MS/MS method was developed and validated to determine caffeine and its major metabolites in plasma of premature infants.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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