Keck Bradly D, Ognibene Ted, Vogel John S
Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason OH 45040, USA.
Bioanalysis. 2010 Mar;2(3):469-85. doi: 10.4155/bio.10.14.
The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of (14)C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the (14)C label), stable across samples storage conditions for at least 1 year, linear over four orders of magnitude with an analytical range from 0.1 Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was excellent (between 1 and 3%), while precision expressed as coefficient of variation was between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of (14)C, respectively (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with (14)C corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a sensitive, accurate and precise method of measuring drug compounds in biological matrices.
对药物分析的验证参数进行了研究，用于独立于化学分离程序的加速器质谱法测量（14）C/C 比。同位素比测量具有特异性（由于（14）C 标记），在样品储存条件下至少 1 年内稳定，在四个数量级上呈线性，分析范围为 0.1 现代至至少 2000 现代（因仪器而异）。此外，准确度极佳（在 1%至 3%之间），而以变异系数表示的精密度在 1%至 6%之间，主要由放射性碳含量和分析样品所花费的时间决定。以检测限和定量下限表示的灵敏度分别为 1 和 10 阿托摩尔（14）C（可表示为化合物当量），对于以 10%的比例掺入（14）C 的典型小分子，相当于 30 fg 当量。加速器质谱法提供了一种灵敏、准确且精密的方法来测量生物基质中的药物化合物。
