Dipartimento di Scienze Biomediche, Facoltà di Medicina e Chirurgia, Università di Foggia, Viale L. Pinto, 1, 71100-Foggia, Italy.
Analyst. 2010 Apr;135(4):789-96. doi: 10.1039/b919622f.
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.
这里提出了一种快速灵敏的方法,涉及大气压热解化学电离质谱(APTDCI-MS),用于 Smith-Lemli-Opitz 综合征(SLOS)的特定实验室筛选,这是一种胆固醇生物合成的遗传性缺陷。SLOS 患者血液中的生化发现是胆固醇(Chol)低,7-和 8-脱氢胆固醇(DHCs)水平高,DHCs/Chol 比值高。所提出的 APTDCI 方法能够直接从干燥的血浆/血斑中离子化甾醇进行定性和定量分析。优化了 APTDCI 参数 - 去溶剂化气流和温度 - 通过分析在玻璃载玻片上点样的 Chol、7-DHC 和胆甾醇硬脂酸标准品来获得正离子模式下的全扫描光谱。通过所提出的方法获得的未受影响对照者(n = 23)干燥血浆斑点中的 Chol 水平与酶法(y = 0.9166x + 0.3811; r = 0.8831)进行了比较,而 SLOS 患者的 Chol 和 DHCs 则与气相色谱火焰离子化检测(GC-FID)方法进行了比较(y = 0.8214x + 0.7388; r = 0.8288)。APTDCI-MS 方法还能够通过直接分析点在纸上的全血和洗涤红细胞来区分正常和 SLOS 样本。总之,APTDCI-MS 方法用于甾醇分析的内在分析高通量可能有助于筛选 SLO 综合征。