Development of analytical methods for the determination of sub-ppm concentrations of palladium and iron in methotrexate.

Analytical methods for limit test (1 microgg(-1)) determination of iron and palladium in the drug substance methotrexate (MTX) were developed. The methods developed were based on microwave-assisted, vapor-phase digestion using quartz inserts inside the digestion vessels, followed by instrumental determination. Iron was determined by graphite furnace atomic absorption spectrometry (GFAAS) and palladium by direct current plasma optical emission spectrometry (DCP-OES). Detection limits of 0.20 microgg(-1) for iron by GFAAS and 0.30 microgg(-1) for palladium by DCP-OES in MTX were obtained. The validity of the methods was studied by spike recovery tests and by analyzing certified reference material (NIST 8433 corn bran, Fe determination) and an organometallic compound ([(C(6)H(5))(3)P](2)PdCl(2), Pd determination). In addition, the specificity of the GFAAS technique for iron determination was confirmed by comparing the results obtained by GFAAS with those obtained by hexapole collision cell, inductively coupled plasma mass spectrometry (ICP-MS).