URINARY-EXCRETION OF 2,3-DINOR-THROMBOXANE B-1, A MAJOR METABOLITE OF THROMBOXANE B-2 IN THE RAT

Urinary 2,3-dinor-thromboxane B-2 (2,3-dinor-TXB(2)), an enzymatic degradation product of TXB(2), is currently measured for evaluating in vivo thromboxane biosynthesis in rats. We simultaneously measured 2,3-dinor-TXB(2) and 2,3-dinor-TXB(1), another product of TXB(2) metabolism, in the urine of rats by immunoaffinity extraction/gas chromatography negative ion chemical ionization mass spectrometry (GC-NICIMS). In rats under basal conditions, urinary excretion of 2,3-dinor-TXB(1) was much higher than that of 2,3-dinor-TXB(2) (19.22+/-4.86 and 1.64+/-0.29 ng/24 h, respectively). The relative abundance of the two metabolites in each animal was fairly constant (91.9+/-1.6 and 8.1+/-1.6% of their sum, respectively). Urinary excretion of both 2,3-dinor-TXB(1) and 2,3-dinor-TXB(2) increased in rats undergoing in vivo hepatic ischemia-reperfusion. Other thromboxane metabolites, including 11-dehydro-TXB(2) and 11-dehydro-2,3-dinor-TXB(2), were measured by GC-NICIMS in selected urines. The resulting profile was: 2,3,4,5-tetranor-TXB(1) > 2,3-dinor-TXB(1) >> 11-dehydro-TXB(2) > 2,3-dinor-TXB(2) = TXB(2). This study shows that urinary 2,3-dinor-TXB(1) is a suitable parameter of TXB(2) biosynthesis in vivo in rats. The possible cross-reactivity of 2,3-dinor-TXB(1) in immunoassays of urinary 2,3-dinor-TXB(2) or even TXB(2) in rats should be considered in future studies.