New HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma.
A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of plasma concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple protein precipitation extraction procedure was applied on 250 microl of plasma aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water + formic acid 0.05%) on a C18 reverse phase analytical column with 20min of analytical run, at flow rate of 1 ml/min. Mean intra-day and inter-day precision for all compounds were 4.3 and 11.4%; mean accuracy was 1.5%; extraction recovery ranged within 95 and 114%. Calibration curves ranged from 10,000 to 62.5 ng/ml. The limit of quantification was set at 78.1 ng/ml for imatinib and at 62.5 ng/ml for dasatinib and nilotinib. This novel developed methodology allows a specific, sensitive and reliable simultaneous determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in plasma of patients affected by chronic myeloid leukemia.
De Francia
Silvia
S
Department of Biological and Clinical Sciences, University of Torino, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy. silvia.defrancia@unito.it
D'Avolio
Antonio
A
De Martino
Francesca
F
Pirro
Elisa
E
Baietto
Lorena
L
Siccardi
Marco
M
Simiele
Marco
M
Racca
Silvia
S
Saglio
Giuseppe
G
Di Carlo
Francesco
F
Di Perri
Giovanni
G
D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy; D013058:Mass Spectrometry / Q000379:methods*; D010879:Piperazines / Q000097:blood*; D047428:Protein Kinase Inhibitors / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000097:blood*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib