Jemal M, Ouyang Z
Bristol-Myers Squibb, New Brunswick, NJ 08903-0191, USA.
J Chromatogr B Biomed Sci Appl. 1998 May 29;709(2):233-41. doi: 10.1016/s0378-4347(98)00080-2.
A capillary gas chromatography-mass spectrometric (GC-MS) method in human urine has been developed and validated for the quantitative determination of dicarboxylic acids (dioic acids) which are produced in the body as a consequence of the administration of an inhibitor of the enzyme squalene synthase, which is involved in the biosynthesis of cholesterol. The standards and quality control (QC) samples were prepared by adding dioic acids into human urine. Internal standard (sebacic acid) was added to each urine sample (0.1 ml) and then dried by evaporation under nitrogen. The dried sample was reacted with pentafluorobenzyl (PFB) bromide under conditions that maximized the formation of the di-PFB ester (at the expense of the mono-PFB ester) of the dioic acids. After drying by evaporation, each sample residue was reconstituted in mesitylene and injected into a capillary GC-MS system via a splitless injection. The detection was by negative ion chemical ionization mass spectrometry with selected ion monitoring (SIM) of the [M-PFB]- of the analytes and the internal standard.
已开发并验证了一种用于人尿中毛细管气相色谱 - 质谱（GC - MS）的方法，用于定量测定二羧酸（二元酸）。这些二羧酸是由于给予参与胆固醇生物合成的角鲨烯合酶抑制剂而在体内产生的。标准品和质量控制（QC）样品通过向人尿中添加二元酸来制备。向每个尿样（0.1 ml）中加入内标（癸二酸），然后在氮气下蒸发干燥。干燥后的样品在使二元酸的二 - 五氟苄基（PFB）酯形成最大化（以牺牲单 - PFB酯为代价）的条件下与五氟苄基（PFB）溴反应。蒸发干燥后，每个样品残渣用均三甲苯复溶，并通过不分流进样注入毛细管GC - MS系统。通过负离子化学电离质谱法进行检测，对分析物和内标的[M - PFB] - 进行选择离子监测（SIM）。
