Determination of ruthenium originating from the investigational anti-cancer drug NAMI-A in human plasma ultrafiltrate, plasma, and urine by inductively coupled plasma mass spectrometry

• Published in: Rapid communications in mass spectrometry Vol. 21; no. 9; pp. 1521 - 1530
• Main Authors: Brouwers, Elke E. M., Tibben, Matthijs M., Rosing, Hilde, Schellens, Jan H. M., Beijnen, Jos H.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2007
• Subjects: Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - urine; Area Under Curve; Dimethyl Sulfoxide - analogs & derivatives; Dimethyl Sulfoxide - blood; Dimethyl Sulfoxide - pharmacokinetics; Dimethyl Sulfoxide - urine; Half-Life; Humans; Mass Spectrometry - methods; Organometallic Compounds - blood; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - urine; Reproducibility of Results; Ruthenium - analysis
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.2985

We present a highly sensitive, rapid method for the determination of ruthenium originating from the investigational anti‐cancer drug NAMI‐A in human plasma ultrafiltrate, plasma, and urine. The method is based on the quantification of ruthenium by inductively coupled plasma mass spectrometry and allows quantification of 30 ng L−1 ruthenium in plasma ultrafiltrate and urine, and 75 ng L−1 ruthenium in human plasma, in 150 µL of matrix. The sample pretreatment procedure is straightforward and only involves dilution with appropriate diluents. The performance of the method, in terms of accuracy and precision, fulfilled the most recent FDA guidelines for bioanalytical method validation. Validated ranges of quantification were 30.0 to 1 × 104 ng L−1 for ruthenium in plasma ultrafiltrate and urine and 75.0 to 1 × 104 ng L−1 for ruthenium in plasma. The applicability of the method and its superiority to atomic‐absorption spectrometry were demonstrated in two patients who were treated with intravenous NAMI‐A in a phase I trial. The assay is now successfully used to support pharmacokinetic studies in cancer patients treated with NAMI‐A. Copyright © 2007 John Wiley & Sons, Ltd.