ISOTOPE DILUTION GC & MS OF TRICYCLIC ANTIDEPRESSANT DRUGS

同位素稀释 GC

• 批准号: 6118607
• 负责人: BARBARA WAY
• 金额: $ 0.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118607
• 关键词: biological products; biomedical resource; child (0-11); drug /agent; female; nervous system; spectrometry; technology /technique

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.

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 对于定量下限的每种分析物 高达1500 ng/mL，与HPLC测量结果相关性良好。 的 GC-MS分析的变异系数为9.7 ± 11.3 分析物放在一起考虑。 虽然在以下情况下观察到干扰 HPLC测定法、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。