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.

Abstract

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

• Authors: Giuseppe Paglia, Oceania D'Apolito, Monica Gelzo, Antonio Dello Russo, Gaetano Corso
• Journal: The Analyst (Analyst) Vol. 135 Issue 4 Pg. 789-96 (Apr 2010) ISSN: 1364-5528 [Electronic] England
• PMID: 20349543 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cholestadienols
• Dehydrocholesterols
• Sterols
• cholesta-5,8-dien-3 beta-ol
• 7-dehydrocholesterol

Topics

• Cholestadienols (blood, chemistry)
• Dehydrocholesterols (blood, chemistry)
• Humans
• Smith-Lemli-Opitz Syndrome (diagnosis)
• Spectrometry, Mass, Electrospray Ionization (methods)
• Sterols (blood, chemistry)