TY - JOUR
T1 - Measurement of serum 7α-hydroxy-4-cholesten-3-one (or 7αC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry
AU - Camilleri, M.
AU - Nadeau, A.
AU - Tremaine, W. J.
AU - Lamsam, J.
AU - Burton, D.
AU - Odunsi, S.
AU - Sweetser, S.
AU - Singh, R.
PY - 2009/7
Y1 - 2009/7
N2 - Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7α-hydroxy-4-cholesten-3-one (7αHCO or 7αC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the 75SeHCAT retention test. Our aim was to develop a serum 7αC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL-1, sensitivity (lowest limit of detection 0.04 ng mL-1), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL-1. There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7αC4 values, and identified increased 7αC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.
AB - Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7α-hydroxy-4-cholesten-3-one (7αHCO or 7αC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the 75SeHCAT retention test. Our aim was to develop a serum 7αC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL-1, sensitivity (lowest limit of detection 0.04 ng mL-1), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL-1. There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7αC4 values, and identified increased 7αC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.
KW - 7α-hydroxy-4-cholesten-3-one
KW - Bile acid retention
KW - SeHCAT
UR - http://www.scopus.com/inward/record.url?scp=67650480494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650480494&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2982.2009.01288.x
DO - 10.1111/j.1365-2982.2009.01288.x
M3 - Article
C2 - 19368662
AN - SCOPUS:67650480494
SN - 1350-1925
VL - 21
SP - 734-e43
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 7
ER -