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  • Title: Improved method to determine succinylacetone in dried blood spots for diagnosis of tyrosinemia type 1 using UPLC-MS/MS.
    Author: Al-Dirbashi OY, Rashed MS, Jacob M, Al-Ahaideb LY, Al-Amoudi M, Rahbeeni Z, Al-Sayed MM, Al-Hassnan Z, Al-Owain M, Al-Zeidan H.
    Journal: Biomed Chromatogr; 2008 Nov; 22(11):1181-5. PubMed ID: 18651606.
    Abstract:
    We describe an improved diagnostic method for tyrosinemia type 1 based on quantifying succinylacetone in dried blood spots by ultra-performance liquid chromatography tandem mass spectrometry. Succinylacetone extracted from a single 3/16 inch disk of specimen collection paper containing a dried blood spot was derivatized with dansylhydrazine, separated on an Acquity UPLC BEH C(18) column (2.1 x 50 mm, 1.7 microm) and detected by electrospray ionization tandem mass spectrometry. Succinylacetone derivative eluted at 0.6 min with a complete run time of 1 min. Using a 13C4 labeled succinylacetone as an internal standard, the calibration plot was linear up to 100 micromol/L with a detection limit (S/N = 3) of 0.2 micromol/L. Intra-day (n = 13) and inter-day (n = 10) variations were better than 10%. The cutoff level of succinylacetone in dried blood spots from healthy infants obtained by the current method was 0.63 micromol/L (n = 151). In dried blood spots from patients with established tyrosinemia type 1 (n = 11), concentration of succinylacetone was 6.4-30.8 micromol/L.
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