ISOTOPE DILUTION GAS CHROMAT MASS SPECT MEASURE OF TRICYCLIC ANTIDEPRESSANT

稳定同位素稀释气相色谱-质谱 （GC-MS）测量三环类抗抑郁药（TCA）是一种有用的方法。 高效液相色谱（HPLC）方法的替代方法 当干扰物质妨碍HPLC准确定量时。 为了进行满意的GC-MS分析，仲胺TCA必须是 衍生的 常用的三氟乙酰基和七氟丁酰基 衍生物相对不稳定，并导致快速恶化， 毛细管气相色谱（GC）柱。 因此，我们研究了 4-乙氧羰基六氟丁酰氯（CHFB-Cl）作为替代品 衍生剂，并开发了稳定同位素稀释GC-MS 使用环标记的[2 H 4]-地昔帕明和[2 H 4]-丙咪嗪的方法 允许测量地昔帕明的内标， 血浆样本中的去甲替林、丙咪嗪和阿米替林 含有这些分析物中的一种或全部。 GC-MS分析呈线性 对于定量下限（25 ng/mL）以上的每种分析物 至1500 ng/mL，并与HPLC测量结果良好相关。 的GC-MS 所有分析物的分析变异系数为9.7 ± 11.3 一起考虑。 尽管在HPLC中观察到干扰 含量测定，硫利达嗪，奋乃静，环苯扎林，或 去甲环苯扎林不干扰TCA的GC-MS测量 在这里检查。 CHFB二阶导数的稳定性 胺TCA被认为是上级的三氟乙酰基 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 quantitation 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 quantit ation (25 ng/mL) 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.