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 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 microM NAMI-A for plasma and urine, and 0.22-44 microM for plasma ultrafiltrate. The lower limit of detection was 0.85 microM in plasma and urine and 0.17 microM in plasma ultrafiltrate. The lower limit of quantitation was 1.1 and 0.22 microM, 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.
Dept. of Pharmacy and Pharmacology, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apmcr@slz.nl
M
M
Crul
H J
HJ
van den Bongard
M M
MM
Tibben
O
O
van Tellingen
G
G
Sava
J H
JH
Schellens
J H
JH
Beijnen
D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002021:Buffers; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D006851:Hydrochloric Acid; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012428:Ruthenium / Q000493:pharmacokinetics; D017975:Ruthenium Compounds; D013054:Spectrophotometry, Atomic
D000970:Antineoplastic Agents; D002021:Buffers; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D006851:Hydrochloric Acid; D004121:Dimethyl Sulfoxide