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Development and validation of a LC-MS/MS method for the quantification of novel therapeutic TT-478, a selective adenosine receptor 2B antagonist, for a phase I/II clinical trial

Lookup NU author(s): Dr Shelby BarnettORCiD, Professor Gareth VealORCiD

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Abstract

© 2025 Informa UK Limited, trading as Taylor & Francis Group.Background: TT-478 is a novel adenosine receptor 2B antagonist, administered orally as a prodrug (TT-702) for the treatment of advanced metastatic prostate cancer in a Phase I/II clinical trial setting. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was required to quantify TT-478 in plasma samples obtained from patients recruited to the ongoing early-phase trial. Methods and results: An LC-MS/MS method has been developed and fully validated that allows the quantification of TT-478 in patient plasma samples following a simple extraction procedure using acetonitrile. The assay was shown to be sensitive and selective for TT-478, with an analytical range of 75−25,000 ng/mL, and exhibited excellent precision (coefficient of variation < 12%) and accuracy in the range of 96–107%. Consistently high recovery was achieved, and no matrix effect observed. Analysis of patient samples confirmed that TT-702 rapidly and completely hydrolyzes to TT-478 following administration. Conclusion: A novel robust method to quantify TT-478 in human plasma has been fully validated and is currently being utilized in an ongoing clinical trial. Analysis of TT-478 levels in plasma samples from these patients will provide first-in-human pharmacokinetic data for this novel compound

Publication metadata

Author(s): Whitaker D, Francis F, Karaborni S, Smith S, Craigen JL, Svetlik S, Barnett S, Veal GJ

Publication type: Article

Publication status: Published

Journal: Bioanalysis

Year: 2025

Volume: 17

Issue: 17

Pages: 1105-1112

Online publication date: 17/10/2025

Acceptance date: 21/08/2025

ISSN (print): 1757-6180

ISSN (electronic): 1757-6199

Publisher: Taylor & Francis

URL: https://doi.org/10.1080/17576180.2025.2554564

DOI: 10.1080/17576180.2025.2554564

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