ISOTOPE DILUTION GC & MS OF TRICYCLIC ANTIDEPRESSANT DRUGS

稳定同位素稀释气相色谱-质谱法 (GC-MS)测定三环抗抑郁药(TCA)是一种有用的方法 高效液相色谱分析法的替代方法 当干扰物质影响高效液相色谱准确定量时。 为了进行满意的GC-MS分析，仲胺TCA必须 派生化的。常用的三氟乙酰和七氟丁酰基 衍生品相对不稳定，会导致快速恶化 毛细管气相色谱柱。因此，我们研究了 4-甲氧基六氟丁酰氯(CHFB-Cl)作为替代品 并开发了稳定的同位素稀释气相色谱-质谱法 使用环标记的[2H4]-地昔帕明和[2H4]-丙咪嗪的方法 允许测量地塞帕明的内部标准， 去甲替林、丙咪嗪和阿米替林在血浆样本中的浓度 含有这些分析物中的一种或全部。GC-MS分析线性关系良好 对于定量下限中的每个分析物 最高可达1500 ng/mL，并与高效液相色谱测量结果有很好的相关性。这个 GC-MS分析变异系数为9.7±1.3%。 分析物放在一起考虑。尽管在以下位置观察到干涉 高效液相色谱法、硫代咪嗪、奋乃静、环苯扎平、或 去甲环苯扎平不干扰三氯乙酸的GC-MS测定 在这里检查过了。二阶CHFB导数的稳定性 发现三氯乙酸胺优于三氟乙酰 这些化合物的衍生物。

Stable isotope dilution gas chromatographic-mass spectrometric (GC-MS) measurement of tricyclic antidepressants (TCA) is a useful alternative to high performance liquid chromatographic (HPLC) methods when interfering substances prevent accurate quantification by HPLC. For satisfactory GC-MS analysis, secondary amine TCA must be derivatized. Commonly employed trifluoroacetyl and heptafluorobutyryl derivatives are relatively unstable and cause rapid deterioration of capillary gas chromatography (GC) columns. We have therefore examined 4-carbethoxyhexafluorobutyryl chloride (CHFB-Cl) as an alternate derivatizing agent and have developed a stable isotope dilution GC-MS method employing ring-labeled [2H4]-desipramine and [2H4]-imipramine internal standards which permits measurement of desipramine, nortriptyline, imipramine, and amitriptyline in plasma samples containing one or all of these analytes. The GC-MS assay is linear for each analyte from the lower limit of quantification up to 1500 ng/mL and correlates well with HPLC measurements. The GC-MS analytic coefficient of variation was 9.7 1 1.3% for all analytes considered together. Although interferences are observed in the HPLC assay, thioridazine, perphenazine, cyclobenzaprine, or norcyclobenzaprine do not interfere with GC-MS measurements of the TCA examined here. The stability of the CHFB derivative of secondary amine TCA was found to be superior to that of the trifluoroacetyl derivatives of these compounds.