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This study evaluated the urinary metabolism of ursodeoxycholic acid (UDCA) by measuring 7β-N-acetylglucosaminide and 3α-sulfate composition in neonates to adolescents using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). We obtained urine from 13 babies, corrected gestational age (CGA) 37-70 weeks, receiving UDCA to treat cholestasis due to total parenteral nutrition (TPN) and 8 patients, aged from 9 months to 15 years, who were treated with oral UDCA administration. The ratios of each UDCA conjugate to total UDCA were as follows : at CGA 37-42 weeks : nonamidated and glycineor taurineamidated ursodeoxycholic acid (UDCAs): 44.0 ±8.0% (mean ± SD), UDCAs 3α-sulfate (UDCAs-3S): 37.8 ± 10.1%, UDCAs 7 β-N-acetylglucosaminide (UDCAs-7NAG): 18.1 ± 14.9% ; at 9 months-3years : UDCAs : 15.7 ± 23.2%, UDCAs-3S : 37.2 ± 8.8%, UDCAs-7NAG : 47.0 ± 22.1%. The ratios of UDCAs-3S and UDCAs-7NAG increased gradually between the ages of 5 and 15 years, as follows : UDCAs, 2.2 ± 1.3% ; UDCAs-3S, 51.2 ± 22.9% ; and, UDCAs-7NAG, 46.6 ± 22.6%. The ratio of 3-sulfooxy-7-N-acetylglucosaminylUDCAs (UDCAs-3S-7NAG) lowered by 0.2% per each age group. Urinary UDCAs-7NAG was not detectable in 2 of 21 patients, who were thus considered to have 7β-hydroxy bile acid N-acetylglucosaminyl transferase (UGT3A1) deficiency. The enzyme activity of N-acetylglucosaminyl transferase to UDCAs was at the same degree as sulfotransferase to UDCAs in early neonates, but reached the adult values by 3-5 years.

Transition of Urinary Ursodeoxycholic Acid 7β-N-acetylglucosaminide and 3α-sulfate from Neonates to Adolescents Using LC/ESI-MS/MS Analysis