Study of transaldolase deficiency in urine samples by capillary LC‐MS/MS

Transaldolase (TAL) is a key enzyme of the pentose phosphate pathway (PPP). TAL deficiency is a newly recognized cause of liver cirrhosis. We have developed an ion‐pair LC separation combined with negative ion electrospray MS/MS detection method to assess PPP metabolites in urine samples from TAL‐deficient mice. Sedoheptulose 7‐phosphate (S7P), C5‐polyols D ‐arabitol and D ‐ribitol, and 6‐phosphogluconate (6PG) levels were markedly increased in urine of TAL‐deficient mice with respect to those of wild‐type and heterozygote littermates. The detection limits of S7P, D ‐arabitol, and 6PG were 0.15 ± 0.015 pmol, 3.5 ± 0.41 pmol, and 0.61 ± 0.055 pmol, respectively. The limit of quantitation was 0.4 ± 0.024 nmol/ml for S7P, 1.6 ± 0.11 nmol/ml for 6PG and 10 ± 0.7 nmol/ml for D ‐arabitol. Additional metabolites, hexose 6‐phosphates ( m / z 259), D ‐ribose 5‐phosphate and D ‐xylulose 5‐phosphate ( m / z 229), D‐ fructose 1,6‐diphosphate ( m / z 339), C6‐polyols ( m / z 181) and GSSG ( m / z 611), that have been positively identified in mouse urine, showed similar levels in control and TAL‐deficient mice. Copyright © 2006 John Wiley & Sons, Ltd.