Tandem mass spectrometric assay of succinylacetone in urine for the diagnosis of hepatorenal tyrosinemia

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography–tandem mass spectrometry

“…In agreement with previous reports this trend is likely due to the increase of creatinine excretion with age [5,[13][14][15][16]. We defined the limits of OA reference intervals between the 1st %ile and 99th %ile, although in clinical practice the 99th %ile limit is mostly of interest.…”

“…To date, since Ito et al [21] described a LC-ESI-MS/MS method for a large number of urinary metabolites, including OA, others have proposed a more specific, high-throughput, sensitive stable-isotope-dilution LC-ESI-MS/MS method for the determination of urinary OA and intermediate metabolites in urine specimens [6,15,22]. Even though reference intervals of urinary OA obtained by LC-ESI-MS/MS are comparable to those reported in this study by HILIC-ESI-MS/MS, our reference limits are narrower and well overlapped with those obtained by stable isotope GC-MS methods [5,16].…”

“…Baker (Deventer, The Netherlands). OA standard was purchased from Sigma-Aldrich (Steinheim, Germany), and [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] N 2 ]-OA, used as internal standard (IS), was purchased from Cambridge Isotope Laboratories (Andover, MA, USA). Filter paper for DBS preparation was of grade 903 and was purchased from Whatman GmbH (Dassel, Germany).…”

Significant increase of succinylacetone within the first 12 h of life in hereditary tyrosinemia type 1

“…Its measurement is a simple method, but not easy to apply in a first tear, high-throughput setting for neonatal screening laboratories [18]. To overcome these problems, new assays for determination of succinylacetone in dried blood spots and urine by flow injection tandem mass spectrometry have been developed in recent years [1,2,9,12,14,16,21], making also analytically succinylacetone the ideal marker for expanded newborn screening for HT1. Exemplary, succinylacetone can be extracted from dried blood spots with an acetonitrile and water solution (80:20 by volume) containing formic acid and hydrazine hydrate (both at 0.1% by volume) and be analyzed by tandem mass spectrometry with a total run time per sample under 2 min [2,16].…”

Hepatosplenomegaly in an 8-Month-Old Child

“…Measurement of SA in blood or urine, however, offers the greatest diagnostic specificity. 22,23 Due to the high incidence of HTI in some regions of Quebec, Canada, that province's newborn screening program includes evaluation of SA by GC-MS using dried blood spots from individuals with elevated tyrosine levels. A similar approach to identifying affected newborns is being considered by some states in the United States for inclusion in their newborn screening programs.…”