Validated method for the determination of the novel organoruthenium anticancer drug NAMI-A in human biological fluids by Zeeman atomic absorption spectrometry

NAMI-A is a novel ruthenium-containing experimental anticancer agent. We have developed and validated a rapid and sensitive analytical method to determine NAMI-A in human plasma, plasma ultrafiltrate and urine using atomic absorption spectrometry with Zeeman correction. The sample pretreatment procedure is straightforward, involving only dilution with an appropriate hydrochloric acid buffer-solution. Because the response signal of the spectrometer depended on the composition of the sample matrix, in particular on the amount of human plasma in the sample, all unknown samples were diluted to match the matrix composition in which the standard line was prepared (plasma-buffer 1: 10 v/v). This procedure enabled the measurement of samples of different biological matrices in a single run. The validated range of determination was 1.1-220 mu M NAMI-A for plasma and urine, and 0.22-44 mu M for plasma ultrafiltrate. The lower limit of detection was 0.85 mu M in plasma and urine and 0.17 mu M in plasma ultrafiltrate. The lower limit of quantitation was 1.1 and 0.22 mu M, respectively. The performance of the method, in terms of precision and accuracy, was according to the generally accepted criteria for validation of analytical methodologies. The applicability of the method was demonstrated in a patient who was treated in a pharmacokinetic phase I trial with intravenous NAMI-A.