title: Quantification of Kryptofix 2.2.2 in [18F]fluorine-labelled radiopharmaceuticals by rapid-resolution liquid chromatography.
abstract: OBJECTIVE
  The cryptand Kryptofix 2.2.2 is used extensively as a phase-transfer reagent in the preparation of [18F]fluoride-labelled radiopharmaceuticals. However, it has considerable acute toxicity. The aim of this study was to develop and validate a method for rapid (within 1 min), specific and sensitive quantification of Kryptofix 2.2.2 at trace levels.
  
  
  METHODS
  Chromatographic separations were carried out by rapid-resolution liquid chromatography (Agilent ZORBAX SB-C18 rapid-resolution column, 2.1 × 30 mm, 3.5 μm). Tandem mass spectra were acquired using a triple quadrupole mass spectrometer equipped with an electrospray ionization interface. Quantitative mass spectrometric analysis was conducted in positive ion mode and multiple reaction monitoring mode for the m/z 377.3 → 114.1 transition for Kryptofix 2.2.2. The external standard method was used for quantification.
  
  
  RESULTS
  The method met the precision and efficiency requirements for PET radiopharmaceuticals, providing satisfactory results for specificity, matrix effect, stability, linearity (0.5-100 ng/ml, r(2)=0.9975), precision (coefficient of variation < 5%), accuracy (relative error < ± 3%), sensitivity (lower limit of quantification=0.5 ng) and detection time (<1 min). Fluorodeoxyglucose (n=6) was analysed, and the Kryptofix 2.2.2 content was found to be well below the maximum permissible levels approved by the US Food and Drug Administration.
  
  
  CONCLUSIONS
  The developed method has a short analysis time (<1 min) and high sensitivity (lower limit of quantification=0.5 ng/ml) and can be successfully applied to rapid quantification of Kryptofix 2.2.2 at trace levels in fluorodeoxyglucose. This method could also be applied to other [18F]fluorine-labelled radiopharmaceuticals that use Kryptofix 2.2.2 as a phase-transfer reagent.
authors.affiliation: PET/CT Center, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, People's Republic of China.
authors.forename: Yexing
authors.initials: Y
authors.lastname: Lao
authors.forename: Cuiping
authors.initials: C
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Manquan
authors.initials: M
authors.lastname: Gan
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Su
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D006801:Humans; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C006071:cryptating agent 222