Goto J
Pharmaceutical Institute, Tohoku University, Sendai, Japan.
Yakugaku Zasshi. 1990 Nov;110(11):807-21. doi: 10.1248/yakushi1947.110.11_807.
Separation and determination of bile acids in biological fluids by high-performance liquid chromatography are reviewed. The capacity ratios of bile acids on an ODS column were affected by the number, position and configuration of the hydroxyl group on the steroid nucleus, and the chromatographic behavior was markedly influenced by the pH of a mobile phase according to the conjugated form at C-24. A new pre-column derivatization reagent, 1-anthroyl nitrile, was developed and applied to the analysis of bile acids in biological fluids. Bile acids were derivatized through the 3 alpha-hydroxyl group into the corresponding esters, separated on an ODS column, and monitored by a fluorescence detector with detection limit of 20 fmol. The sensitive method for the determination of bile acids in biological materials by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is also described. Of various derivatives for the carboxyl group, the pentafluorobenzyl (PFB) ester provided the highest value of the ratio of the negative to positive ion current. A characteristic carboxylate anion [M-181]- was produced as the most abundant ion by the loss of the PFB group in NICI. PFB esters of bile acids were further derivatized into the dimethylethylsilyl ethers and then separated by GC. The detection limit was 2 fg when the characteristic anion was monitored in the NICI mode. The preparation of 18O-labelled bile acids, as the internal standard for the trace analysis or the tracer for the metabolic study, was developed. Finally, the clean-up procedure for bile acids in biological fluids was investigated. The combined use of solid-phase extraction with a Sep-pak C18 or Bond Elut cartridge and group separation on a lipophilic ion-exchange gel, piperidinohydroxypropyl Sephadex LH-20, was found most effective for this purpose.
综述了高效液相色谱法分离和测定生物体液中胆汁酸的方法。胆汁酸在ODS柱上的容量比受甾体核上羟基的数量、位置和构型影响,且根据C-24位的共轭形式,流动相的pH对色谱行为有显著影响。开发了一种新型柱前衍生试剂1-蒽腈,并将其应用于生物体液中胆汁酸的分析。胆汁酸通过3α-羟基衍生为相应的酯,在ODS柱上分离,并用荧光检测器监测,检测限为20 fmol。还描述了气相色谱(GC)结合负离子化学电离(NICI)质谱法测定生物材料中胆汁酸的灵敏方法。在各种羧基衍生物中,五氟苄基(PFB)酯的负离子与正离子电流比值最高。在NICI中,通过PFB基团的损失产生特征性羧酸根阴离子[M-181]-作为最丰富的离子。胆汁酸的PFB酯进一步衍生为二甲基乙基硅醚,然后通过GC分离。在NICI模式下监测特征阴离子时,检测限为2 fg。开发了18O标记胆汁酸的制备方法,用于痕量分析的内标或代谢研究的示踪剂。最后,研究了生物体液中胆汁酸的净化程序。发现将Sep-pak C18或Bond Elut柱进行固相萃取与在亲脂性离子交换凝胶哌啶羟丙基葡聚糖LH-20上进行分组分离联合使用,对该目的最为有效。