A highly reproducible method for the measurement of [6‐O‐methyl‐11C]diprenorphine and its radio‐metabolites based on solid‐phase extraction and radio‐high‐pressure liquid chromatography. (3rd November 2020)

• Record Type: Journal Article
• Authors: Fairclough, Michael; McMahon, Adam; Barnett, Elizabeth; Matthews, Julian; Brown, Christopher A.; Jones, Anthony
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 64:Number 1(2021)
• Page Start: 30
• Page End: 39
• Publication Date: 2020-11-03
• Subjects: C‐11 -- HPLC -- metabolites -- PET -- SPE -- [11C]Diprenorphine; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3886
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Described here is a method for the measurement of the radio‐metabolites of the positron emission tomography radiotracer [6‐ O‐ methyl‐ 11 C]diprenorphine ([ 11 C]diprenorphine) using in‐line solid‐phase extraction (SPE) combined with radio‐high‐pressure liquid chromatography analysis. We believe that this method offers a reliable and reproducible approach to [ 11 C]diprenorphine metabolite analysis. In addition, different SPE stationary phases are assessed for their efficiency for loading, retention and elution of the parent molecule and its metabolites. Having assessed C4, phenyl and C18 stationary phase, we concluded that a C18 SPE was optimal for our method. Finally, in silico predictions of diprenorphine metabolism were compared with in vivo metabolism of [ 11 C]diprenorphine induced by hepatic microsomal digestion and analysed by matrix‐assisted laser desorption/ionisation mass spectrometry. It was found that there was a high degree of agreement between the two methods and in particular the formation of the diprenorphine‐3‐glucuronide metabolite. Abstract : A reliable and reproducible approach to the measurement of the radio‐metabolites of the positron emission tomography (PET) radiotracer [6‐ O ‐methyl‐ 11 C]diprenorphine ([ 11 C]diprenorphine) is described. The method makes use of an in‐line solid phase extraction (SPE) system combined with radio‐HPLC analysis. SPE is used to extract and concentrate [ 11 C]diprenorphine and its radio‐metabolites before analysis by analytical HPLC. Using this robust approach, 11 C radio‐metabolites can be successfully quantified with minimal sample loss.