TY - JOUR
T1 - LC/ESI-MS/MS analysis of urinary 3β-sulfooxy-7β-N- acetylglucosaminyl- 5-cholen-24-oic acid and its amides
T2 - New biomarkers for the detection of Niemann-Pick type C disease
AU - Maekawa, Masamitsu
AU - Misawa, Yasushi
AU - Sotoura, Ayako
AU - Yamaguchi, Hiroaki
AU - Togawa, Masami
AU - Ohno, Kousaku
AU - Nittono, Hiroshi
AU - Kakiyama, Genta
AU - Iida, Takashi
AU - Hofmann, Alan F.
AU - Goto, Junichi
AU - Shimada, Miki
AU - Mano, Nariyasu
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - We developed a sensitive, reliable, and accurate LC/ESI-MS/MS method for measurement of 3β-sulfooxy- 7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine amides in urine. This atypical C24 bile acid has been reported previously to be present in the urine of patients with Niemann-Pick Type C (NPC) disease. In the method, targeted analytes are concentrated at the front edge of a trapping column, Shim-pack MAYI-C8, which permits elimination of contaminating molecules in the urinary matrix. The trapped analytes are then eluted, separated on a YMC-Pack Pro C18, and quantified with MS/MS using selected reaction monitoring. The method could detect (as amount injected) 2 pg of nonamidated 3b-sulfooxy- 7b-N-acetylglucosaminyl-5-cholen-24-oic acid, 2 pg of its glycine-amide, and 0.6 pg of its taurineamide, and is linear up to 300 pg. The method was then used to measure the three analytes in the urine of NPC patients (N = 2), 3b-hydroxysteroid dehydrogenase deficiency patients (N = 2), and healthy volunteers (N = 8). Measurable concentrations of all three analytes were present in all subjects. The urinary concentration of the sum of all three analytes was four hundred times greater in the 3 month NPC patient and 40 times greater in the adult patient than that of healthy volunteers. The markedly elevated urinary concentration of 3b-sulfooxy-7b-N-acetylglucosaminyl-5-cholen-24-oic acid and its amides in NPC patients suggests that these compounds may be valuable biomarkers for detection of NPC disease.
AB - We developed a sensitive, reliable, and accurate LC/ESI-MS/MS method for measurement of 3β-sulfooxy- 7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine amides in urine. This atypical C24 bile acid has been reported previously to be present in the urine of patients with Niemann-Pick Type C (NPC) disease. In the method, targeted analytes are concentrated at the front edge of a trapping column, Shim-pack MAYI-C8, which permits elimination of contaminating molecules in the urinary matrix. The trapped analytes are then eluted, separated on a YMC-Pack Pro C18, and quantified with MS/MS using selected reaction monitoring. The method could detect (as amount injected) 2 pg of nonamidated 3b-sulfooxy- 7b-N-acetylglucosaminyl-5-cholen-24-oic acid, 2 pg of its glycine-amide, and 0.6 pg of its taurineamide, and is linear up to 300 pg. The method was then used to measure the three analytes in the urine of NPC patients (N = 2), 3b-hydroxysteroid dehydrogenase deficiency patients (N = 2), and healthy volunteers (N = 8). Measurable concentrations of all three analytes were present in all subjects. The urinary concentration of the sum of all three analytes was four hundred times greater in the 3 month NPC patient and 40 times greater in the adult patient than that of healthy volunteers. The markedly elevated urinary concentration of 3b-sulfooxy-7b-N-acetylglucosaminyl-5-cholen-24-oic acid and its amides in NPC patients suggests that these compounds may be valuable biomarkers for detection of NPC disease.
KW - Biomarker
KW - LC/ESI-MS/MS
KW - Multiple conjugate
KW - Niemann-Pick type C disease
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UR - http://www.scopus.com/inward/citedby.url?scp=84885000878&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2013.05.017
DO - 10.1016/j.steroids.2013.05.017
M3 - Article
C2 - 23751200
AN - SCOPUS:84885000878
VL - 78
SP - 967
EP - 972
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 10
ER -