Imatinib assay by HPLC with photodiode-array UV detection in plasma from patients with chronic myeloid leukemia: Comparison with LC-MS/MS.
BACKGROUND
Imatinib, a competitive inhibitor of BCR-ABL tyrosine kinase, is now the first-line treatment for chronic myelogenous leukemia (CML). Therapeutic drug monitoring targeting trough plasma levels of about 1000ng/mL may help to optimize the therapeutic effect.


METHODS
We developed a high-performance liquid chromatography (HPLC) method with UV/Diode Array Detection (DAD) for trough imatinib concentration determination in human plasma. Imatinib trough levels were measured in plasma from 65 CML patients using our method and LC-MS/MS as the reference method. Results with these two methods were compared using Deming regression, chi-square test, and sign test.


RESULTS
The calibration curve was prepared in blank human plasma. HPLC-UV/DAD calibration curves were linear from 80 to 4000ng/mL, and the limit of quantification was set at 80ng/mL. The between-day variation was 6.1% with greater than 96% recovery after direct plasma deproteinization and greater than 98% recovery from the column. No significant differences in imatinib plasma levels were found between HPLC-UV/DAD and LC-MS/MS.


CONCLUSIONS
This HPLC-UV/DAD method was sufficiently specific and sensitive for imatinib TDM, with no evidence of interference. Our rapid inexpensive HPLC-UV/DAD method that requires only widely available equipment performs well for plasma imatinib assays.
Centre Hospitalier de Versailles, Service de Pharmacie, Le Chesnay, France.
Olivia
O
Roth
Odile
O
Spreux-Varoquaux
Stephane
S
Bouchet
Philippe
P
Rousselot
Sylvie
S
Castaigne
Sophie
S
Rigaudeau
Victoria
V
Raggueneau
Patrice
P
Therond
Philippe
P
Devillier
Mathieu
M
Molimard
Benjamin
B
Maneglier
D001549:Benzamides; D001774:Blood Chemical Analysis / Q000191:economics / Q000295:instrumentation / Q000379:methods*; D001798:Blood Proteins / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D004553:Electric Conductivity; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007755:Laboratories, Hospital; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000302:isolation & purification; D011743:Pyrimidines / Q000097:blood* / Q000302:isolation & purification; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
D001549:Benzamides; D001798:Blood Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate