Quantitative analysis of D-24851, a novel anticancer agent, in human plasma and urine by liquid chromatography coupled with tandem mass spectrometry.
The development of a liquid chromatography/tandem mass spectrometric assay for the quantitative analysis of the novel tubulin inhibitor D-24851 in human plasma and urine is described. D-24851 and the deuterated internal standard were extracted from 250 microL of plasma or urine using hexane/ether (1:1, v/v). Subsequently, 10-microL aliquots of reconstituted extracts were injected onto an Inertsil ODS analytical column (50 x 2.0 mm i.d., 5 microm particle size). An eluent consisting of methanol/5 mM ammonium acetate, 0.004% formic acid in water (80:20, v/v) was pumped at a flow rate of 0.2 mL/min. An API 365 triple quadrupole mass spectrometer was used in the multiple reaction monitoring mode for sensitive detection. For human plasma a dynamic range of 1-1000 ng/mL was validated, and for human urine a range of 0.25-50 ng/mL. Validation was performed according to the most recent FDA guidelines and all results were within requirements. The assay has been successfully applied to support a phase I clinical trial with orally administered D-24851.
Stokvis
Ellen
E
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apess@slz.nl
Nan-Offeringa
Lianda G A H
LG
Ouwehand
Mariët
M
Tibben
Matthijs M
MM
Rosing
Hilde
H
Schnaars
Yvonne
Y
Grigat
Martina
M
Romeis
Peter
P
Schellens
Jan H M
JH
Beijnen
Jos H
JH
D000081:Acetamides / Q000097:blood* / Q000652:urine*; D000970:Antineoplastic Agents / Q000097:blood* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000652:urine*; D013058:Mass Spectrometry; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results
D000081:Acetamides; D000970:Antineoplastic Agents; D007211:Indoles; C419187:indibulin