Rapid Detection of the Residual Kryptofix 2.2.2 Levels in [¹⁸F]-Labeled Radiopharmaceuticals by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Abstract

A fast and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC/MS/MS) method was developed and validated for determination of the residual levels of Kryptofix 2.2.2 (K222) in [¹⁸F]-labeled radiopharmaceuticals. The analytical time was only 3 min, and the injection volume was 5 μL. An electrospray ionization source was used in the positive mode (ESI⁺) for UPLC/MS/MS. The analytical measurements were performed in the multiple reaction monitoring (MRM) mode. The calibration curve at the spiked concentrations of 2–500 ng/mL for K222 showed good linearity. The intra- and inter-day precisions were not more than 5%. The accuracy satisfied the requirement of quality control analysis, the recoveries were found to be 80–120%. This method was successfully applied to detect the residue of K222 in [¹⁸F]-fluorodeoxyglucose [(¹⁸F)FDG], [¹⁸F]-fluoromisonizole[(¹⁸F)FMISO], 3′-deoxy-3′-[¹⁸F]-fluorothymidine [(¹⁸F)FLT], and two new [¹⁸F]-labeled radiopharmaceuticals 4-[-(2-[¹⁸F]fluoroethoxy) methyl]-1-[2-(2-methyl-5-nitro-1H- imidazol-1-yl) ethyl]-1H-1,2,3-triazole (named as ¹⁸F-BNU-1) and 4-[-(2-[¹⁸F] fluoroethoxy) methyl]-1-[2-(2-nitro-1H-imidazol-1-yl) ethyl]-1H-1,2,3-triazole (named as ¹⁸F-BNU-2) produced in our lab.

Keywords:

• [¹⁸F]-labeled PET radiopharmaceuticals
• Kryptofix 2.2.2
• Quality control
• UPLC/MS/MS

Acknowledgments

The authors are grateful to the financial support from the National 863 Program (2006AA02A408) and Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period (2008BAI55B05).