Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry
| Autor: | Jeffrey W. Meeusen, Leslie J. Donato, Michael Camilleri, Alan J. Lueke, Stacy M. Kenyon |
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| Rok vydání: | 2017 |
| Předmět: |
Diarrhea
Serum medicine.medical_specialty Constipation medicine.drug_class Clinical Biochemistry Ion suppression in liquid chromatography–mass spectrometry Gastroenterology Sensitivity and Specificity Mass Spectrometry Bile Acids and Salts 03 medical and health sciences Feces 0302 clinical medicine Tandem Mass Spectrometry Internal medicine medicine Protein precipitation Humans Irritable bowel syndrome Cholestenones Gastrointestinal tract Bile acid Chemistry Bile acid malabsorption General Medicine medicine.disease Steatorrhea Endocrinology 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology medicine.symptom Chromatography Liquid |
| Zdroj: | Clinical biochemistry. 52 |
| ISSN: | 1873-2933 |
| Popis: | Background Imbalance of bile acids (BA) homeostasis in the gastrointestinal tract can lead to chronic diarrhea or constipation when BA in the colon are in excess or low, respectively. Since both disturbances of bowel function can result from other etiologies, identifying BA imbalance is important to tailor treatment strategies. Serum concentrations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4), a precursor in bile acid synthesis, reflect BA homeostasis. Here we describe a method to accurately measure serum 7aC4 and evaluate the clinical utility in patients with diarrhea or constipation phenotypes. Methods Serum 7aC4 is measured after acetonitrile protein precipitation using C18 liquid chromatography, tandem mass spectrometry , and deuterium-labeled 7aC4 internal standard. Assay performance including linearity, precision, and accuracy was assessed using waste serum samples. The reference interval was established in healthy individuals without BA-altering conditions or medications. Clinical performance was assessed in patients with irritable bowel syndrome . Results The method precisely and accurately measured 7aC4 in human serum from 1.4–338 ng/mL with no ion suppression or interference from related 7-keto-cholesterol. Central 95th percentile reference interval was 2.5–63.2 ng/mL. Lower serum 7aC4 was found in patients with constipation with sensitivity/specificity of 79%/55% compared to healthy controls. Higher 7aC4 was found in patients with bile acid diarrhea (BAD) compared to those without BAD with sensitivity/specificity of 82%/53%. Conclusions We have developed a sensitive and precise assay for measuring the concentration of 7aC4 in serum. The assay can be used to screen for diarrhea caused by bile acid malabsorption. |
| Databáze: | OpenAIRE |
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