title: A new HPLC-UV validated method for therapeutic drug monitoring of tyrosine kinase inhibitors in leukemic patients.
abstract: Development and validation of simple, rapid, and reliable high-performance liquid chromatography (HPLC)-UV method for quantification of major tyrosine kinase inhibitors, imatinib, dasatinib, and nilotinib, in human plasma is presented. Chromatographic separation of the drugs is  achieved on an RP-C(18) column at flow rate of 0.9 mL/min at 35°C; eluate is monitored at 267 nm. Mean intra-day and inter-day precision for all compounds are 2.5 and 13.3%; mean accuracy is 13.9%; extraction recovery ranges within 40.24 and 81.81%. Calibration curves range from  10 to 0.005 μg/mL. Limits of detection are 10 ng/mL for imatinib and nilotinib, 50 ng/mL for dasatinib; limits of quantitation are 50 ng/mL for imatinib and nilotinib, 100 ng/mL for dasatinib. Although this method allows the detection of dasatinib, levels found in patients plasma are close  to the limit of detection, then below the limit of quantitation. Quantification with HPLC-mass spectrometry, then, is required for dasatinib to give a correct evaluation. In conclusion, the sensitivity of this new method is sufficient to perform therapeutic monitoring and pharmacokinetic  studies of imatinib and nilotinib but not dasatinib in CML patients.
authors.affiliation: Clinical Pharmacology, Clinical and Biological Sciences Department, University of Turin, S. Luigi Hospital, Orbassano, TO, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pirro
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.forename: Francesca
authors.initials: F
authors.lastname: De Martino
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Stefano
authors.initials: S
authors.lastname: Ulisciani
authors.forename: Giovanna Rege
authors.initials: GR
authors.lastname: Cambrin
authors.forename: Silvia
authors.initials: S
authors.lastname: Racca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Carlo
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000627:therapeutic use; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000069439:Dasatinib; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy; D016014:Linear Models; D010879:Piperazines / Q000097:blood / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000097:blood / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000097:blood / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib