Busker E, Günther K, Martens J
J Chromatogr. 1985 Dec 20;350(1):179-85. doi: 10.1016/s0021-9673(01)93517-4.
The enantiomeric purity of the pharmaceutical D-penicillamine (I) has been determined by a novel high-performance liquid chromatographic technique involving the formation of 5,5-dimethylthiazolidine-4-carboxylic acid (III) by reaction of I with formaldehyde and separation of the optical antipodes by means of ligand exchange chromatography using the copper(II) complex of (2S,4R,2'RS)-4-hydroxy-1-(2'-hydroxydodecyl)proline, which is coated on a reversed-phase column. The limit of determination for the L-antipode is ca. 0.1%. The validation of the method is accomplished by comparison with an independent gas chromatographic procedure. Thirteen commercially available lots of I are shown to be of equally high enantiomeric purity (ca. 99.9%).
通过一种新型高效液相色谱技术测定了药物D-青霉胺（I）的对映体纯度，该技术包括I与甲醛反应形成5,5-二甲基噻唑烷-4-羧酸（III），并使用涂覆在反相柱上的(2S,4R,2'RS)-4-羟基-1-(2'-羟基十二烷基)脯氨酸的铜(II)配合物通过配体交换色谱法分离光学对映体。L-对映体的测定限约为0.1%。通过与独立的气相色谱法比较完成了该方法的验证。结果表明，13个市售批次的I具有同样高的对映体纯度（约99.9%）。
