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
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
复制标题
DOI：
10.1039/b919622f
复制
发表时间：
2010-01-01
期刊：
影响因子：
4.2
通讯作者：
Corso, Gaetano
中科院分区：
文献类型：
--
作者：
Paglia, Giuseppe;D'Apolito, Oceania;Corso, Gaetano
本文提出了一种快速、灵敏的方法，包括大气压热解吸化学电离质谱（APTDCI-MS），用于特异性实验室筛查Smith-Lemli-Opitz综合征（SLOS），一种遗传性胆固醇生物合成缺陷。SLOS患者血液中的生化发现是低胆固醇（Chol）、高7-和8-脱氢胆固醇（DHCs）水平和高DHCs/Chol比率。APTDCI提出的方法能够直接从干燥的血浆/血斑中提取甾醇进行定性和定量分析。对关键的APTDCI参数-去溶剂化气体流量和温度-进行了优化，分析了点在载玻片上的Chol、7-DHC和硬脂酸胆固醇酯标准品，以正离子模式获取全扫描光谱。用本法与酶法比较了未受影响的对照组（n = 23）的干血浆斑点中的Chol水平（y = 0.9166x + 0.3811;用气相色谱-火焰离子化检测法（GC-FID）测定SLOS患者血清中Chol和DHCs含量（y = 0.8214x + 0.7388; r = 0.8288）。APTDCI-MS方法还能够直接分析全血和在纸上斑点的洗涤红细胞来区分正常和SLOS样品。结论：本研究所建立的高通量APTDCI-MS方法可用于SLO综合征的筛查。
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.