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![Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59557.jpg&w=3840&q=50)
Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941
Published on: April 28, 2019
Development and validation of an LC-MS/MS method for the quantification of novel therapeutic TT-478, a selective
Daniel Whitaker1, Laura Francis1, Sami Karaborni2
1Newcastle Cancer Centre Pharmacology Group, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
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.Clinical trial registration: https://clinicaltrials.gov/study/NCT05272709?term=AREA%5BConditionSearch%5D(Advanced%20Prostate%20Cancer)%20AND%20AREA%5BBasicSearch%5D(phase%203%20drug)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING%20OR%20ENROLLING_BY_INVITATION%20OR%20ACTIVE_NOT_RECRUITING)&rank=10 identifier is NCT05272709.
Insights
A new LC-MS/MS method quantifies TT-478, an adenosine receptor 2B antagonist, in patient plasma. This supports pharmacokinetic analysis for advanced prostate cancer treatment.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- TT-478 is a novel adenosine receptor 2B antagonist.
- Administered orally as a prodrug (TT-702) for advanced metastatic prostate cancer.
- A Phase I/II clinical trial is ongoing.
Purpose of the Study:
- To develop and validate a sensitive LC-MS/MS method.
- To quantify TT-478 in human plasma samples from patients.
- To support pharmacokinetic analysis in early-phase clinical trials.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Simple acetonitrile extraction of plasma samples.
- Method validation for sensitivity, selectivity, accuracy, and precision.
Main Results:
- The LC-MS/MS method is sensitive and selective for TT-478.
- Analytical range: 75-25,000 ng/mL.
- High accuracy (96-107%) and precision (<12% CV) were achieved.
- TT-702 rapidly and completely hydrolyzes to TT-478 in vivo.
Conclusions:
- A robust and validated LC-MS/MS method for TT-478 quantification in human plasma is established.
- The method is currently used in an ongoing clinical trial.
- Analysis will provide first-in-human pharmacokinetic data for TT-478.
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