ISOTOPE DILUTION GAS CHROMAT MASS SPECT MEASURE OF TRICYCLIC ANTIDEPRESSANT

三环类抗抑郁药的同位素稀释气相色谱质谱测定

• 批准号: 6665899
• 负责人: BARBARA WAY
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665899
• 关键词: biomedical resource; biotechnology; human tissue; nucleic acids; spectrometry

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.

稳定同位素稀释气相色谱-质谱联用 (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。 为了获得令人满意的 GC-MS 分析，仲胺 TCA 必须是 衍生化。 常用的有三氟乙酰基和七氟丁酰基 衍生物相对不稳定，会导致快速恶化 毛细管气相色谱 (GC) 柱。 因此我们研究了 4-乙酯基六氟丁酰氯 (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[2H4]-地昔帕明和[2H4]-丙咪嗪的方法 允许测量地昔帕明的内部标准， 血浆样本中的去甲替林、丙咪嗪和阿米替林 含有一种或所有这些分析物。 GC-MS 测定呈线性 对于每种分析物，从定量下限 (25 ng/mL) 开始 高达 1500 ng/mL，并且与 HPLC 测量值具有良好的相关性。 气相色谱-质谱联用仪 所有分析物的分析变异系数为 9.7 1 1.3% 一起考虑。 尽管在 HPLC 中观察到干扰 测定，硫利达嗪，奋乃静，环苯扎林，或 去甲环苯扎林不会干扰 TCA 的 GC-MS 测量 在这里检查。 二阶CHFB导数的稳定性 发现胺 TCA 优于三氟乙酰基 这些化合物的衍生物。