A highly reproducible method for the measurement of [6‐ O ‐methyl‐ 11 C]diprenorphine and its radio‐metabolites based on solid‐phase extraction and radio‐high‐pressure liquid chromatography,Journal of Labelled Compounds and Radiopharmaceuticals

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A highly reproducible method for the measurement of [6‐ O ‐methyl‐ 11 C]diprenorphine and its radio‐metabolites based on solid‐phase extraction and radio‐high‐pressure liquid chromatography
Journal of Labelled Compounds and Radiopharmaceuticals ( IF 0.9 ) Pub Date : 2020-11-03 , DOI: 10.1002/jlcr.3886
Michael Fairclough ₁ , Adam McMahon ₁ , Elizabeth Barnett ₁ , Julian Matthews ₁ , Christopher A Brown ₂ , Anthony Jones _{3,

4}

Affiliation

Described here is a method for the measurement of the radio-metabolites of the positron emission tomography (PET) radiotracer [6-O-methyl-11 C]diprenorphine ([11 C]diprenorphine) using in-line solid phase extraction (SPE) combined with radio-HPLC 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 MALDI 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.

中文翻译：

基于固相萃取和射频高压液相色谱的高度重复性的[6-O-甲基-11C]二丙诺啡及其放射性代谢物的测量方法

这里描述的是一种使用在线固相萃取 (SPE) 测量正电子发射断层扫描 (PET) 放射性示踪剂 [6-O-甲基-11 C]二丙诺啡 ([11 C]二丙诺啡) 的放射性代谢物的方法结合放射性 HPLC 分析。我们相信该方法为[11 C]二丙诺啡代谢物分析提供了可靠且可重复的方法。此外，还评估了不同 SPE 固定相加载、保留和洗脱母体分子及其代谢物的效率。对 C4、苯基和 C18 固定相进行评估后，我们得出结论，C18 SPE 最适合我们的方法。最后，将二丙诺啡代谢的计算机预测与肝微粒体消化诱导的[11 C]二丙诺啡体内代谢进行比较，并通过 MALDI 质谱法进行分析。结果发现，两种方法之间存在高度一致性，特别是二丙诺啡-3-葡萄糖醛酸代谢物的形成。

更新日期：2020-11-03

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