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The need for a reliable oxytocin assay

Molecular Psychiatry volume 26, pages 6107–6108 (2021)Cite this article

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We have read with interest the recent review on the topic of intranasal oxytocin research [1] and the review in another journal by the same lead author on this topic [2]. The reviews are excellent but would benefit from, in our opinion, an extended discussion of the well-known problems with the assay of oxytocin [3, 4]. Irrespective of the route of oxytocin delivery, whether intranasal, intravenous or any other, the ability to reliably assay its level in the blood, cerebrospinal fluid or saliva is a vital component to interpreting any potential biological effects.

The lack of an accurate assay is likely due to a combination of poor recovery of oxytocin from samples, the presence of oxytocin in a variety of forms (i.e., free, protein-bound, and adhering to cellular components), unreliable assays (e.g., antibodies with poorly defined epitopes), and possible cross-reactivity of antibodies with components other than oxytocin. For this reason, much has been written about sample preparation techniques, such as the need for extraction of oxytocin [5]. Even when extraction is used, the blood levels of oxytocin reported in the published literature vary by 2–3 orders of magnitude [6]. The gold-standard approach for quantitative assay of peptides and other molecules of biomedical interest is stable isotope dilution mass spectrometry. This approach is not only rigorously quantitative, the structure of the analyte is also indisputable, since there are multiple reference points for compound identification, such as consistency of chromatographic retention time of extracted analyte and quantification standard, coelution of extracted analyte with the stable isotope labelled internal standard, precursor mass and isotope profile, and fragment masses for primary sequence confirmation. Such an approach has previously been reported in the literature [7], but quantitative mass spectrometry is rarely applied in work reporting the biological effects of oxytocin. Perhaps for ease-of-use, most of the published work on oxytocin is founded on antibodies and ELISA assays, where considerable doubt about the epitope exists, poor correlation between available methods is reported [8, 9], and it is almost certainly one of the main reasons for the poor reproducibility.

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References

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Authors and Affiliations

  1. Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW, Australia

    Anne Poljak & Perminder Sachdev

  2. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia

    Anne Poljak

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  1. Anne Poljak
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Correspondence to Anne Poljak.

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Poljak, A., Sachdev, P. The need for a reliable oxytocin assay. Mol Psychiatry 26, 6107–6108 (2021). https://doi.org/10.1038/s41380-021-01114-0

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