Abstract

Objectives

7α-Hydroxy-4-cholesten-3-one (C4) is the common intermediary of both primary bile acids. C4 is recommended by the British Society of Gastroenterology for the investigation of bile acid diarrhoea (BAD) in patients with chronic diarrhoea. This project aimed to develop and validate an assay to quantitate C4 in serum and assess the stability of C4 in unseparated blood.

Methods

Accuracy was underpinned by calibrating to quantitative nuclear magnetic resonance analysis. C4 was analysed in a 96-well plate format with a deuterated C4 internal standard and liquid-liquid extraction. Validation followed the 2018 Food and Drug Administration guidelines. To assess C4 stability, healthy volunteers (n=12) donated 8 fasted samples each. Samples were incubated at 20 °C for up to 72 h and retrieved, centrifuged, aliquoted and frozen for storage at different time points prior to C4 analysis.

Results

The C4 method demonstrated excellent analytical performance and passed all validation criteria. The method was found to be accurate, precise, free from matrix effects and interference. After 72 h of delayed sample separation, C4 concentration gradually declined by up to 14 % from baseline. However, the change was not significant for up to 12 h.

Conclusions

We present a robust method of analysing serum C4, offering a convenient alternative to ⁷⁵SeHCAT for BAD investigation. C4 was found to decline in unseparated blood over time; however, after 12 h the mean change was <5 % from baseline. Our results suggest C4 is suitable for collection from both primary and secondary care prior to gastroenterology referral.

• Book : 63(1)
• Pub. Date : 2025
• Page : pp.154-163
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The Low Level Waste Repository in West Cumbria requires, as part of their environmental safety case, a geological model to support hydrogeological understanding and future development of the site. A range of legacy data accrued over the last 60 years exists, which is characterised by variable data collection methods, formats, and quality. The geological model development process is atypical due to this large body of existing data and the requirements of the ESC, resulting in an initial primarily observational digital geological model. Outlined here is the approach undertaken for geological model development and includes terminology, data management practices, and considers the role of conceptualisation and it's direct application to the observational 3D digital model when there is significant existing observational data. Sites with significant legacy data and atypical requirements may be more common in the future, as more site investigations are completed and data are shared. The process applied is a development of Peter Fookes' work, highlighting the importance of the conceptual model, but that application of conceptual ideas to the development of 3D digital geological models may look different in a world of increasing observational data.

• Book : 30(1)
• Pub. Date : 2025
• Page : pp.egsp30-2024-19
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