Analytical Research and Development, Pharmaceutical Science, Worldwide Research & Development, Pfizer Inc. Groton, CT 06340, USA.
J Pharm Biomed Anal. 2012 Mar 25;62:17-22. doi: 10.1016/j.jpba.2011.12.020. Epub 2012 Jan 16.
The control of residual metals in active pharmaceutical ingredients (API's) and intermediates is critical because of their potential toxic effects. A variety of technologies are available to measure residual metals in pharmaceutical compounds including, AAS, ICP-AES, and ICP-MS. The newest technology is total reflectance X-ray fluorescence spectroscopy (TXRF) which uses primary X-rays to excite atoms which then emit secondary X-rays. The emitted X-rays are characteristic of the individual elements present, and the intensities of the emitted X-rays are proportional to the concentrations of the elements present in the sample. The benefits of TXRF are that it is essentially unaffected by matrix effects, is very sensitive (ppb's), requires small amounts of sample (5-10 mg), and requires very little sample preparation time. During this study, TXRF was used to quantitatively measure residual metals in API's and intermediates and such topics as sample preparation, sensitivity, linearity, reproducibility and accuracy are discussed. The results obtained by TXRF were compared with those obtained by ICP-MS for the same samples for Pd and Cu measurement, and statistical analysis indicated that the results obtained by the two technologies are equivalent at the 95% confidence level. A comparison is also made of the capabilities of the instruments using a tungsten (W) or a molybdenum (Mo) source for excitation. Both instruments could be used for the quantitative determination of residual metals in pharmaceuticals.
原料药（API）和中间体中残留金属的控制至关重要，因为它们可能具有毒性作用。有多种技术可用于测量药物化合物中的残留金属，包括原子吸收光谱法（AAS）、电感耦合等离子体发射光谱法（ICP-AES）和电感耦合等离子体质谱法（ICP-MS）。最新的技术是全反射 X 射线荧光光谱法（TXRF），它使用初级 X 射线激发原子，然后原子发射次级 X 射线。发射的 X 射线是存在的各个元素的特征，发射的 X 射线的强度与样品中存在的元素的浓度成正比。TXRF 的优点是基本上不受基质效应的影响，非常灵敏（ppb），需要的样品量很少（5-10 毫克），并且需要很少的样品制备时间。在这项研究中，TXRF 用于定量测量 API 和中间体中的残留金属，讨论了样品制备、灵敏度、线性、重现性和准确性等主题。将 TXRF 获得的结果与相同样品的 ICP-MS 获得的结果进行了比较，对于 Pd 和 Cu 的测量，统计分析表明，这两种技术的结果在 95%置信水平下是等效的。还比较了使用钨（W）或钼（Mo）源激发的仪器的性能。这两种仪器都可用于定量测定药物中的残留金属。
