A validated UPLC–MS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma

Zeng, Jing; Cai, Hua Lin; Jiang, Zhi ping; Wang, Qing; Zhu, Yan; Xu, Ping; Zhao, Xie lan

doi:10.1016/j.jpha.2017.07.009

Cited by 27 publications

(11 citation statements)

References 23 publications

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“…Several studies described the LC-MS/MS-based detection method of dasatinib in plasma. [17][18][19] Although these studies developed determination methods for dasatinib with high sensitivity and accuracy, liquid-liquid extraction and solid-phase extraction were chosen for sample…”

Section: Discussionmentioning

confidence: 99%

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Yang¹,

Zhang²,

Wang³

et al. 2021

DDDT

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Background and Aim: Dasatinib is approved for the treatment of leukaemia worldwide.Triazole agents such as posaconazole may be used for the control of secondary fungal infection with leukaemia. This work aimed to develop a bioanalytical method to study the potential interaction between dasatinib and posaconazole. Methods: An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was established to measure the plasma concentrations of dasatinib and posaconazole in rats simultaneously. Simple protein precipitation with acetonitrile was applied to extract dasatinib and posaconazole in samples. The chromatographic separation of analytes was conducted on an UPLC BEH C18 column using a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile. Dasatinib and posaconazole were monitored in positive ion mode with the following mass transition pairs: m/z 488.2→401.1 for dasatinib and m/z 701.3→683.4 for posaconazole. The method was successfully applied for pharmacokinetic interaction between dasatinib and posaconazole. Results: The established method expressed good linearity in 1-1000 ng/mL of dasatinib and 5-5000 ng/mL of posaconazole, with limit of detection was 1 ng/mL and 5 ng/mL, respectively. Methodology validations, including accuracy, precision, matrix effect, recovery, and stability, met the US Food and Drug Administration (FDA) acceptance criteria for bioanalytical method validation. Dasatinib strongly inhibited the clearance of posaconazole in vivo, while posaconazole expressed no significant effect on the pharmacokinetics of dasatinib. Conclusion: Dasatinib alters the pharmacokinetics of posaconazole. Attention should be paid to the unexpected risk of adverse clinical outcomes when posaconazole is coadministered with dasatinib.

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Section: Discussionmentioning

confidence: 99%

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Yang¹,

Zhang²,

Wang³

et al. 2021

DDDT

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“…Peripheral blood samples were collected from eligible patients between 21 and 27 hours after the last imatinib administration for plasma trough concentrations. Imatinib plasma concentrations was determined using ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) (Waters, USA), following the reported method previously (20). The internal standard was gliquidone.…”

Section: Sample Collection and Measurement Of Plasma Imatinib Concentmentioning

confidence: 99%

Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia

et al. 2020

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Purpose: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML). Methods: There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration. Complete cytogenetic response (CCyR), major molecular response (MMR) and complete molecular response (CMR) were used as metrics for efficacy. Nine single nucleotide polymorphisms in 5 genes, SLC22A4 (917 T>C, -248 C>G and -538 C>G), SLC22A5 (-945 T>G and -1889 T>C), SLCO1A2 (-361 G>A), SLCO1B3 (334 T>G and 699 G>A) and ABCG2 (421C>A) were selected for genotyping. Results: Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 vs 984.89±454.06 ng mL-1, p<0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 vs 1121.17±527.14 ng mL-1, p=0.007; 1528.00±709.98 vs 1112.67±518.35 ng mL-1, p=0.003, respectively). Carriers of A allele in SLCO1A2 -361G>A achieve higher CCyR and MMR rates (p=0.047, OR=4.320, 95% CI: 0.924-20.206; p=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and SLCO1A2 -361G>A genotypes are independent factors affecting imatinib efficacy. The positive and negative predictive values for CCyR are 71.01% and 68.75%, respectively. The positive and negative predictive values for MMR are 62.86% and 69.70%, respectively. Conclusion: Imatinib trough concentrations and SLCO1A2 -361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML. Keywords: Efficacy, Imatinib, Polymorphisms, Trough concentration

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“…LLE is characterized by clean extraction, of which multiple extraction steps are required to improve the recovery of analytes. SPE is less time-consuming and requires less solvent volume ( Koller et al, 2020 ), which is a more costly method compared with LLE ( Zeng et al, 2017 ). Moreover, Mukai et al employed a supported liquid extraction method using an ISOLUTE SLE+ column which was more convenient compared to SPE ( Mukai et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Drug Monitoring and Individualized Medicine of Dasatinib: Focus on Clinical Pharmacokinetics and Pharmacodynamics

Bian

Shao

et al. 2021

Front. Pharmacol.

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Dasatinib is an oral second-generation tyrosine kinase inhibitor known to be used widely in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Notably, although a high pharmacokinetic variability in patients and an increased risk of pleural effusion are attendant, fixed dosing remains standard practice. Retrospective studies have suggested that dasatinib exposure may be associated with treatment response (efficacy/safety). Therapeutic drug monitoring (TDM) is gradually becoming a practical tool to achieve the goal of individualized medicine for patients receiving targeted drugs. With the help of TDM, these patients who maintain response while have minimum adverse events may achieve long-term survival. This review summaries current knowledge of the clinical pharmacokinetics variation, exposure-response relationships and analytical method for individualized dosing of dasatinib, in particular with respect to therapeutic drug monitoring. In addition, it highlights the emerging insights into several controversial issues in TDM of dasatinib, with the aim of presenting up-to-date evidence for clinical decision-making and insights for future studies.

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A validated UPLC–MS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma

Cited by 27 publications

References 23 publications

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia

Therapeutic Drug Monitoring and Individualized Medicine of Dasatinib: Focus on Clinical Pharmacokinetics and Pharmacodynamics

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