The use of total reflectance X-ray fluorescence (TXRF) for the determination of metals in the pharmaceutical industry.

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.