Abstract: A highperformance liquid chromatographytandem mass spectrometric method (LC/MS/MS) was used to quantify Kryptofix 2.2.2(K_2.2.2) in ¹⁸F-FDG and ¹⁸F-FLT and other ¹⁸F-radiopharmaceuticals. First molecular ion peak m/z 377.4 M+H⁺ were detected by full scan mode, then the daughter ions 114.1, 289.4 and 333.5 m/z were detected by product ion scan mode, the mass scanning mode was set to multiple reaction monitoring (MRM) and programmed to monitor the transitions of the parent/daughter ion pairs of 377.4/114.1, 377.4/289.4 and 377.4/333.5 m/z for K_2.2.2. The calibration curve was established over the range of 20～500 μg/L, the linear correlation coefficient was 0.999 9, the limit of quantitation for K_2.2.2 was 20 μg/L. Reproducibility and accuracy all accorded with expectation. Direct measurement of the concentration of K_2.2.2 in the routine radiopharmaceutical of ¹⁸F-FDG was less than 20 μg/L, and the concentration of K_2.2.2 in 5 batchs ¹⁸F-FLT products were between 0.286 and 16.9 mg/L. Above all, LC/MS/MS is the most sensitive method for the quantification of K_2.2.2 so far.