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

稳定同位素方法与气相色谱-质谱联用被广泛认为是估计生物体液中少量内源性和合成类固醇的最准确和最具体的方法。在这种技术中，使用稳定的同位素标记的类似物作为内标物，在样品处理的所有阶段提供了补偿材料损失的主要优点，而内部标准物与所研究的化合物具有不同的结构，则可能不是这种情况。同位素标记化合物作为示踪剂的使用在代谢研究中也有广泛的应用。该技术的主要优点之一是内源性化合物及其稳定同位素标记的外源性类似物可以很容易地通过质谱法进行区分。我们开发了一种毛细管气相色谱-质谱法，用于同时测定人血浆中的皮质醇、可的松、强的松和泼尼松，使用我们实验室合成的各自的氘酸盐类似物作为内标。该方法已应用于小儿肾病患者泼尼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.