Direct Plasma Metabolite Analysis of Positron Emission Tomography Radioligands by Micellar Liquid Chromatography with Radiometric Detection

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• 作者：Ryuji Nakao ; Magnus Schou ; Christer Halldin
• 刊名：Analytical Chemistry
• 出版年：2012
• 出版时间：April 3, 2012
• 年：2012
• 卷：84
• 期：7
• 页码：3222-3230
• 全文大小：337K
• 年卷期：v.84,no.7(April 3, 2012)
• ISSN：1520-6882

文摘

Determination of radio-metabolites in plasma samples taken during a positron emission tomography (PET) study is an important component in the pharmacokinetic evaluation of PET radioligands. We have developed and validated a new analytical procedure for the plasma metabolite analysis of PET radioligands based on micellar liquid chromatography using an anionic surfactant mobile phase. Chromatographic separation was performed on an octadecyl semipreparative column (10 mm I.D. 脳 160 mm, 10 渭m) using 100 mM sodium dodecyl sulfate (SDS) and 1-butanol in 10 mM sodium-phosphate (pH 7.2) at a flow rate of 5 mL/min. The samples taken from monkey or human plasma during PET measurements were directly injected into a liquid chromatographic (LC) system coupled to an online radiometric detector under micellar conditions using 1鈥?% (v/v) 1-butanol mobile phase to remove plasma proteins and concentrate the analytes at the column head. At 2 min, mobile phase was changed to elute and separate PET radioligand and its radiometabolites with high peak capacity under high submicellar conditions (10鈥?5% 1-butanol). This procedure allowed direct plasma injection (up to 2 mL) into the LC column without any pretreatment with a short analysis-time of 8鈥?0 min. Satisfactory reproducibility, linearity, sensitivity, accuracy and recovery were obtained in the validation study. The developed method was successfully applied to study the metabolism for diverse groups of PET radioligands and provided reliable determination of PET radioligands in human and monkey plasma. This method is advantageous in terms of simplifying and shortening the processes required to analyze short-lived radioligands as well as in providing a more accurate estimation of the metabolite corrected input function, especially for the radioligands with lower recoveries or degradation potential during the deproteination process in a conventional procedure.