Mechanistic Study on the Cortisol Metabolism and Secretion in the Endocrinological Disorders

稳定同位素方法与GC-MS联用被广泛认为是测定生物液中少量内源性和合成类固醇的最准确和最特异的方法。在这项技术中，使用稳定的同位素标记类似物作为内标提供了重大优势，可以比较样品处理所有阶段的物质损失，这可能不是具有与被研究化合物不同结构的内标的情况。使用同位素标记化合物作为示踪剂在代谢研究中也得到了广泛的应用。该技术的主要优点之一是利用质谱仪可以很容易地区分外源性给药的内源性化合物及其稳定的同位素标记类似物。以本实验室合成的氢化物类似物为内标，建立了同时测定人血浆中皮质醇、可的松、强的松龙和泼尼松的毛细管GC-MS方法。该方法已用于1例肾病患儿强的松龙的药代动力学研究。

Stable isotope methodology coupled with GC-MS is widely accepted as the most accurate and specific method for estimation of the small amounts of endogenous and synthetic steroids in biological fluids. In this technique, the use of stable isotopically labeled analogues as internal standards offers major advantages of compasating for losses of material at all stages of sample handling, which may not be the case with internal standards possessing a different structure from the compound under investigation.The use of isotopically labeled compounds as tracers has also enjoyed broad application in metabolic studies. One of the major advantages of this technique is that an endogenous compound and its stable isotopically labeled analogue exogenously administered can be differentiated easily by employing mass spectrometry.We have developed a capillary GC-MS method for the simultaneous assay of cortisol, cortisone, prednisolone, and prednisone in human plasma using their respective deuteratede analogs synthesized in our laboratory as internal standards. The method has been applied for the phamacokinetic study of prednisolone in a pediatric patient with nephrosis.