Voltammetry of 7-dehydrocholesterol as a new and useful tool for Smith-Lemli-Opitz syndrome diagnosis

• Published in: Talanta (Oxford) Vol. 229; p. 122260
• Main Authors: Klouda, Jan, Benešová, Lenka, Kočovský, Pavel, Schwarzová-Pecková, Karolina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2021
• Subjects: 7-dehydrocholesterol; Artificial serum; Bare electrodes; Cholecalciferol; Dehydrocholesterols - analysis; Diamond; Humans; Oxidoreductases Acting on CH-CH Group Donors; Smith-Lemli-Opitz Syndrome - diagnosis; Voltammetry; Bare electrodes; Artificial serum; Voltammetry; 7-dehydrocholesterol; Cholecalciferol
• ISSN: 0039-9140; 1873-3573
• DOI: 10.1016/j.talanta.2021.122260

7-Dehydrocholesterol is an essential biomarker of Smith-Lemli-Opitz syndrome, a congenital autosomal recessive disorder. This study shows for the first time that electrochemical oxidation of 7-dehydrocholesterol can be used for its voltammetric determination. Two classes of supporting electrolytes in acetonitrile and a mixture of acetonitrile-water were used: inorganic acids known to promote structural changes of steroids and indifferent electrolytes. Oxidation of 7-dehydrocholesterol at ca +0.8 V (vs. Ag/AgNO3 in acetonitrile) in 0.1 mol L−1 NaClO4 in acetonitrile is useful for its voltammetric detection using common bare electrode materials. Detection limits for 7-dehydrocholesterol lie in the low micromolar range for all the working electrodes, including boron-doped diamond (0.4 μmol L−1) and disposable thin-film platinum electrodes (0.5 μmol L−1), which are advantageous because of the low volumes of studied solutions. After Bligh-Dyer extraction, quantification of 7-dehydrocholesterol concentration (boron-doped diamond) or concentration range (thin-film platinum) is easily attainable in artificial serum. The mere knowledge of the concentration range provides clinically valuable information, as 7-dehydrocholesterol levels are employed for SLOS diagnosis as a binary criterion (elevated, tens to hundreds μmol L−1 in symptomatic/non-elevated, typically bellow 1 μmol L−1 in healthy individuals in plasma). Moreover, it is shown that 7-dehydrocholesterol (provitamin D3) and cholecalciferol (vitamin D3) can be oxidized in 0.1 mol L−1 HClO4 in acetonitrile. Under these conditions, their voltammetric response changes dramatically, and their oxidation potential difference transiently increases from 0.08 V to 0.25 V, which should facilitate their simultaneous voltammetric determination. This work constitutes a foundation for a reliable and straightforward method for Smith-Lemli-Opitz syndrome diagnosis and monitoring 7-dehydrocholesterol’s biotransformation to cholecalciferol.
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•A voltammetric method for 7-dehydrocholesterol detection proposed for the first time.•7-DHC gives a voltammetric signal at ca +0.8 V on common unmodified electrodes.•Potential for SLOS diagnosis and monitoring of biotransformation to cholecalciferol.•Bligh-Dyer extraction from artificial serum used for determination on BDD electrode.•Estimation of 7-DHC concentration range in artificial serum on-chip Pt electrode.