Direct analysis of sterols from dried plasma/blood spots by an atmospheric pressure thermal desorption chemical ionization mass spectrometry (APTDCI-MS) method for a rapid screening of Smith–Lemli–Opitz syndrome

摘要

Here is proposed a rapid and sensitive method involving atmospheric pressure thermal desorptionnchemical ionization mass spectrometry (APTDCI-MS) for specific laboratory screening of the Smith–nLemli–Opitz syndrome (SLOS), an inherited defect of cholesterol biosynthesis. Biochemical findings innthe blood of SLOS patients are low cholesterol (Chol), high 7- and 8-dehydrocholesterol (DHCs) levelsnand high DHCs/Chol ratios. The APTDCI proposed method is able to ionize sterols for qualitative andnquantitative analysis directly from dried plasma/blood spots. Critical APTDCI parameters –ndesolvation gas flow and temperature – were optimized analyzing Chol, 7-DHC and cholesteryl stearatenstandards spotted onto a glass slide acquiring the full scan spectra in positive ion mode. Chol levels inndried plasma spots of unaffected controls (n ?23) obtained by the proposed method were comparednwith those of the enzymatic method (y ?0.9166x + 0.3811; r ?0.8831) while Chol and DHCs of SLOSnpatients (n ?9) were compared with the gas chromatography flame ionization detection (GC-FID)nmethod (y ?0.8214x + 0.7388; r ?0.8288). The APTDCI-MS method is also able to differentiatennormal from SLOS samples directly analyzing whole blood and washed red cells spotted on paper. Innconclusion, the intrinsic analytical high-throughput of APTDCI-MS method for sterol analysis couldnbe useful to screen SLO syndrome.