Perry J A, Chang M
Regis Chemical Company, Morton Grove, IL 60053.
J Pharm Sci. 1990 May;79(5):437-9. doi: 10.1002/jps.2600790516.
For the treatment of human neuromuscular diseases, 3,4-diaminopyridine (DAP) is six to ten times more effective than 4-aminopyridine (AP), but only half as convulsant and toxic. Therefore, there is a need for the determination of AP in DAP. With only conventional equipment, high-pressure liquid chromatography can be used for the extremely sensitive detection of a trace contaminant under one condition: that is, the trace must be eluted before the major component it contaminates. Prior elution presents a trace peak in a fully exploitable form that is maximally efficient and maximally observable. This has already been demonstrated with a Pirkle-concept chiral stationary phase for determination of a chiral trace. However, its application to determination of a nonchiral trace with a reversed phase has not previously been reported. Such an application is reported here. In this demonstrative study, selectivity and loading capability were iteratively improved. Ion pairing with dodecanesulfonate maximized selectivity. It was again shown that using a less concentrated sample in greater volume maximizes loading capability without obscuring the peak of the trace. Eventually, the ability to detect 0.005% AP in DAP was demonstrated. Whether that sensitivity might be improved still more, perhaps with a larger column, was not established.
对于人类神经肌肉疾病的治疗，3,4 - 二氨基吡啶（DAP）的效果比4 - 氨基吡啶（AP）强六至十倍，但惊厥性和毒性仅为其一半。因此，需要测定DAP中的AP。仅使用常规设备，在一种条件下高压液相色谱法可用于对痕量污染物进行极其灵敏的检测：即痕量必须在其污染的主要成分之前洗脱。提前洗脱会呈现出一个可充分利用的痕量峰，其效率最高且最易于观察。这已经在用于测定手性痕量的Pirkle概念手性固定相上得到了证明。然而，此前尚未报道其在反相条件下用于测定非手性痕量的应用。本文报道了这样一种应用。在这项示范性研究中，选择性和进样量能力得到了反复改进。与十二烷基磺酸盐进行离子配对可使选择性最大化。再次表明，使用浓度较低但体积较大的样品可在不掩盖痕量峰的情况下使进样量能力最大化。最终，证明了能够检测出DAP中0.005%的AP。但未确定是否通过使用更大的色谱柱等方式还能进一步提高这种灵敏度。
