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

NAMI-A is a novel ruthenium-containing experimental anticancer agent. We ha ve developed and validated a rapid and sensitive analytical method to deter mine NAMI-A in human plasma, plasma ultrafiltrate and urine using atomic ab sorption spectrometry with Zeeman correction. The sample pretreatment proce dure is straightforward, involving only dilution with an appropriate hydroc hloric acid buffer-solution. Because the response signal of the spectromete r depended on the composition of the sample matrix, in particular on the am ount of human plasma in the sample, all unknown samples were diluted to mat ch the matrix composition in which the standard line was prepared (plasma-b uffer 1:10 v/v). This procedure enabled the measurement of samples of diffe rent biological matrices in a single run. The validated range of determinat ion was 1.1-220 muM NAMI-A for plasma and urine, and 0.22-1 44 muM for plas ma ultrafiltrate. The lower limit of detection was 0.85 muM in plasma and u rine and 0.17 muM in plasma ultrafiltrate. The lower limit of quantitation was 1.1 and 0.22 muM, respectively. The performance of the method, in terms of precision and accuracy, was according to the generally accepted criteri a for validation of analytical methodologies. The applicability of the meth od was demonstrated in a patient who was treated in a pharmacokinetic phase I trial with intravenous NAMI-A.