Steroidal isomers with uniform mass spectra of their per-TMS derivatives:: Synthesis of 17-hydroxyandrostan-3-ones, androst-1-, and -4-ene-3,17-diols
Steroidal isomers with uniform mass spectra of their per-TMS derivatives:: Synthesis of 17-hydroxyandrostan-3-ones, androst-1-, and -4-ene-3,17-diols
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DOI：
10.1016/j.steroids.2007.03.006
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发表时间：
2007-06-01
期刊：
影响因子：
2.7
通讯作者：
Schaenzer, Wilhelm
中科院分区：
文献类型：
--
作者：
Parr, Maria K.;Zapp, Josef;Schaenzer, Wilhelm
在人体运动兴奋剂控制分析中，大多数类固醇化合物是在糖醛酸类化合物经酶解后以三甲基硅基(TMS)衍生物的形式通过气相色谱-质谱仪(GC-MS)进行分析的。根据世界反兴奋剂机构的建议，分析物的鉴定应以保留时间和质谱学特征为基础。本研究表明，16个C19甾体化合物的双-TMS衍生物，即S-雄烯-L-烯-3xi、17-xi-diol(8个异构体)、雄-4-烯-3xi、17 xi-diol(4个异构体)和17-羟基-5-xi-雄烷-3-酮(4个异构体)的双-TMS衍生物具有非常相似的质谱图。一般来说，当考虑到所有这些异构体的保留时间(以Kovac指数提供)时，限制两到三个可能的异构体是可能的。可靠的鉴定还应包括将分析物的保留时间与同时测量的参考化合物进行比较。在某些情况下，标准加成可能是合适的。由于可获得性有限，上述异构体是通过用K-Selectride还原相应的α，β-不饱和氧代、甾体或通过催化氢化(Pd/C为催化剂)来合成的。反应产物经核磁共振表征，进一步还原为相应的5-雄烷-3-，17-雄烷二醇，并与市售参比标准品进行了GC-MS鉴定。(C)2007 Elsevier Inc.保留所有权利。
In human sports doping control analysis most of the steroids are analyzed after enzymatic hydrolysis of the glucuronides as per-trimethylsilyl (TMS) derivatives applying gas chromatography-mass spectrometry (GC-MS). According to the recommendations of the World Anti-Doping Agency the identification of analytes should be based on retention time and on mass spectrometric characterization. This study shows that the bis-TMS derivatives of 16 specific C19 steroids, namely the stereoisomers of S xi-androst-l-ene-3 xi,17 xi-diol (8 isomers), androst-4-ene-3 xi,17 xi-diol (4 isomers), and 17 xi-hydroxy-5 xi-androstan-3-one (4 isomers), reveal very similar mass spectra. As a rule, when taking the retention times, which are provided as Kovac indices for all these isomers, into account, a restriction to two or three possible isomers is possible. Reliable identification should additionally include a comparison of the retention times of the analytes with the reference compounds measured concomitantly. In some cases standard addition may be appropriate.Due to the limited availability; the above mentioned isomers were synthesized by reduction of the corresponding alpha,beta-unsaturated oxo, steroids either with K-Selectride or by catalytic hydrogenation (Pd/C as catalyst). The products of the reactions were identified by means of nuclear magnetic resonance (NMR) characterization and by further reduction to the corresponding 5 xi-androstane-3 xi,17 xi-diols and GC-MS comparison with commercially available reference standards. (c) 2007 Elsevier Inc. All rights reserved.