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.
Department of Biological and Clinical Sciences, University of Torino, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy. silvia.defrancia@unito.it
Silvia
S
De Francia
Antonio
A
D'Avolio
Francesca
F
De Martino
Elisa
E
Pirro
Lorena
L
Baietto
Marco
M
Siccardi
Marco
M
Simiele
Silvia
S
Racca
Giuseppe
G
Saglio
Francesco
F
Di Carlo
Giovanni
G
Di Perri
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