Detection of Δ4-3-oxo-steroid 5β-reductase deficiency by LC–ESI-MS/MS measurement of urinary bile acids

Muto, Akina; Takei, Hiroyuki; Unno, Atsushi; Murai, Tsuyoshi; Kurosawa, Takao; Ogawa, Shoujiro; Iida, Takashi; Ikegawa, Shigeo; Mori, Jun; Ohtake, Akira; Hoshina, Takayuki; Mizuochi, Tatsuki; Kimura, Akihiko; Hofmann, Alan F.; Hagey, Lee R.; Nittono, Hiroshi

doi:10.1016/j.jchromb.2012.05.023

Cited by 38 publications

(35 citation statements)

References 16 publications

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“…We have also reported a simplifi ed LC-MS method for the quantifi cation of bile acids in human urine ( 17 ), and that technique was modifi ed for fecal bile acids as reported here. The advantage of this technique compared with the HPLC technique herein reported is that the former provides information on a variety of conjugated bile acids that can be present.…”

Section: Discussionmentioning

confidence: 99%

“…The 36 variants of C 24 bile acids, which included the unconjugated, N -acylamidates conjugated with glycine or taurine at C-24 in the side chain, as well as the C-3 sulfated bile acids, were examined. The retention times and transitions used in the selected reaction monitoring (SRM) for the examined bile acids were shown in our previous report ( 17 ). The primary bile acids in the advanced cirrhotic subjects presented not only unconjugated forms but conjugated forms.…”

Section: Lc-esi-ms/ms Analysis Of Fecal Bile Acids In Healthy and Cirmentioning

confidence: 99%

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A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS

Kakiyama

Muto

Takei

et al. 2014

Journal of Lipid Research

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125

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We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1 ) lyophilization of the stool sample; 2 ) reconstitution in buffer and enzymatic deconjugation using cholylglycine hydrolase/sulfatase; 3 ) incubation with 0.1 N NaOH in 50% isopropanol at 60°C to hydrolyze esterifi ed bile acids; 4 ) extraction of bile acids from particulate material using 0.1 N NaOH; 5 ) isolation of deconjugated bile acids by solid phase extraction; 6 ) formation of phenacyl esters by derivatization using phenacyl bromide; and 7 ) HPLC separation measuring eluted peaks at 254 nm.

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Section: Discussionmentioning

confidence: 99%

Section: Lc-esi-ms/ms Analysis Of Fecal Bile Acids In Healthy and Cirmentioning

confidence: 99%

A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS

Kakiyama

Muto

Takei

et al. 2014

Journal of Lipid Research

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125

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“…14 Liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) appears to be the best technique for analysis of urinary conjugated cholesterol metabolites. [15][16][17][18][19] If we have preliminary information on the nature of disease-specific molecules, we should be able to analyse target molecules with high sensitivity by using selected reaction monitoring mode. However, there are many unknown biomarker candidates including molecules for which synthetic reference standards are unavailable.…”

Section: Introductionmentioning

confidence: 99%

Focused metabolomics using liquid chromatography/electrospray ionization tandem mass spectrometry for analysis of urinary conjugated cholesterol metabolites from patients with Niemann–Pick disease type C and 3β-hydroxysteroid dehydrogenase deficiency

et al. 2015

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Background: Various conjugated cholesterol metabolites are excreted in urine of the patients with metabolic abnormalities and hepatobiliary diseases. We aimed to examine the usefulness of precursor ion scan and neutral loss scan for the characterization of conjugated cholesterol metabolites in urine. Methods: A mixture of authentic standards of conjugated cholesterol metabolites was used for investigating the performance of the present method. The urine of patients with Niemann-Pick diseases type C and 3b-hydroxysteroid dehydrogenase deficiency were analysed by precursor ion scan of m/z 97, 74, and 124. Results: A precursor ion scan of m/z 97 was effective for identifying conjugates with ester sulphates on hydroxyl groups whereas ester sulphates on phenolic alcohols were signalled by a neutral loss scan of 80 Da. Monosaccharide-conjugated cholesterol metabolites were signalled by a precursor ion scan of m/z 113. Although precursor ion scan of m/z 74 and 124 was effective for finding glycine-and taurine-conjugated metabolites, high intensity of product ions (m/z 74 and 124) disturbed measurement of other multiply conjugated metabolites. The urine samples contained many conjugated cholesterol metabolites, and there were several disease-specific intense peaks. We found several unknown intense peaks with three known peaks in urine of the Niemann-Pick type C patient. In the patient with 3b-hydroxysteroid dehydrogenase deficiency, intense peaks that were tentatively identified as 5-cholenoic acid sulphates and their glycine and taurine conjugates were present. Conclusion: The method should lead to the discovery of new urinary biomarkers for these disturbances of cholesterol catabolism and transport.

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“…To operate the LC/ESI-MS/MS, the spray voltage and vaporizer temperature were set at 3,500 V and 330 C, respectively. The sheath and auxiliary gas nitrogen pressures were set at 50 and 10 arbitrary units, respectively, and the ion transfer capillary temperature was 330 C. The collision gas argon pressure and the collision energy were kept at 1.3 mm Torr and 27-55 eV, respectively, all in the negative ion mode 19,23 .…”

Section: Lc/esi-ms/ms Analysismentioning

confidence: 99%

“…Those product ions were optimized at m/z 74 for glycine-conjugated bile acids, at m/z 124 for taurine-conjugate bile acids, and at m/z 97 for 3 variants of UDCAs-3S such as bile acid sulfates 19,23 . Whereas UDCAs-7NAG provided UDCA at m/z 391.3, GUDCA-7NAG produced NAG H 2 O at m/z 202.1, TUDCA-7NAG gave M NAG at m/z 480.5, and GUDCA-3S-7NAG gave M SO 3 at m/z 651.6 Table 1 .…”

Section: Lc/esi-ms/ms Analysis Of Unconjugated and Conjugated Udcamentioning

confidence: 99%

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

:筆頭著者

Murai

Kurosawa

et al. 2017

Showa Univ J Med Sci

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: This study evaluated the urinary metabolism of ursodeoxycholic acid UDCA by measuring 7 -N-acetylglucosaminide and 3 -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 glycine-or taurine-amidated ursodeoxycholic acid UDCAs : 44.0 8.0% mean SD , UDCAs 3 -sulfate UDCAs-3S : 37.8 10.1%, UDCAs 7 -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 7 -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.

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Detection of Δ4-3-oxo-steroid 5β-reductase deficiency by LC–ESI-MS/MS measurement of urinary bile acids

Cited by 38 publications

References 16 publications

A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS

A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS

Focused metabolomics using liquid chromatography/electrospray ionization tandem mass spectrometry for analysis of urinary conjugated cholesterol metabolites from patients with Niemann–Pick disease type C and 3β-hydroxysteroid dehydrogenase deficiency

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

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