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

M. Crul*, H. J.G.D. Van Den Bongard, M. M. Tibben, O. Van Tellingen, G. Sava, J. H.M. Schellens, J. H. Beijnen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 μM NAMI-A for plasma and urine, and 0.22-44 μM for plasma ultrafiltrate. The lower limit of detection was 0.85 μM in plasma and urine and 0.17 μM in plasma ultrafiltrate. The lower limit of quantitation was 1.1 and 0.22 μM, 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.

Original languageEnglish
Pages (from-to)442-445
Number of pages4
JournalAnalytical and Bioanalytical Chemistry
Volume369
Issue number5
Publication statusPublished - 1 Mar 2001

Cite this

Crul, M., Van Den Bongard, H. J. G. D., Tibben, M. M., Van Tellingen, O., Sava, G., Schellens, J. H. M., & Beijnen, J. H. (2001). Validated method for the determination of the novel organo-ruthenium anticancer drug NAMI-A in human biological fluids by Zeeman atomic absorption spectrometry. Analytical and Bioanalytical Chemistry, 369(5), 442-445.