Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Rood, Johannes J.M.; Schellens, Jan H.M.; Beijnen, Jos H.; Sparidans, Rolf W.

doi:10.1016/j.jpba.2016.06.037

Cited by 30 publications

(14 citation statements)

References 178 publications

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“…Furthermore, when an acidic ammonium formate solution (pH 3.0) was used as the eluent, the gefitinib peak became sharper. In the literature, a C18 column is typically used for the separation and quantification of tyrosine kinase inhibitors , including gefitinib . However, basic compounds such as gefitinib and volitinib, could be adsorbed to the silica stationary phase in a C18 column, which could then affect the shape of the peak.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC–MS/MS for application to a pharmacokinetic study in rats

Noh

Lee

Kim

et al. 2017

J of Separation Science

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A rapid, simple, and accurate procedure was developed and validated for the simultaneous quantification of two anticancer agents, volitinib and gefitinib in rat plasma by high-performance liquid chromatography with tandem mass spectrometry. The samples were separated by gradient elution from a cyano column within five minutes, using 0.1% formic acid in acetonitrile and 10 mM ammonium formate solution (pH 3.0) as mobile phase. When plasma samples were deproteinated by adding methanol, the analytes in the extract were detected in the positive ionization mode with the tracer ion mass of 346.1 → 145.1 for volitinib and 446.8 → 128.1 for gefitinib. The assay was determined to be valid in the concentration ranges of 2 to 1000 ng/mL for volitinib, and of 1 to 500 ng/mL for gefitinib. Intra- and interday accuracies ranged from 88.0 to 104.7% for volitinib and from 90.3 to 101%, for gefitinib. The precision of the assay ranged from 2.1 to 9.71% for volitinib and 2.31 to 12.1% for gefitinib. This method was successfully applied to a pharmacokinetic study of volitinib and gefitinib after the administration of an intravenous or oral dose, indicating that the developed assay can be used to simultaneously determine the concentrations of volitinib and gefitinib in rat plasma.

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Section: Resultsmentioning

confidence: 99%

Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC–MS/MS for application to a pharmacokinetic study in rats

Noh

Lee

Kim

et al. 2017

J of Separation Science

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“…11,21,22 In literature, the LLOQs of LC-MS/MS assays for smPKI analysis in plasma are most often in the low ng/mL range and based on expected plasma concentrations following administration of a dose at therapeutic strength. 23 For this reason, the published LLOQs might not be reflective of the LLOQs that can be obtained when the limits of sensitivity of LC-MS/MS equipment are explored.…”

Section: Discussionmentioning

confidence: 99%

“…For these drugs, LC-MS/MS assays have been developed with an LLOQ of 2 pg/mL for each drug to analyze abemaciclib-13 C 8 and ibrutinib-13 C 6 drug concentrations following microdose administration. 24 The LLOQs described for the analysis of therapeutic concentrations of these drugs are 0.5 ng/mL for ibrutinib 23 and 1 ng/mL for abemaciclib, 24 indicating the potential to improve the sensitivity of LC-MS/MS assays more than a 100-fold when there is a direct clinical need. In our laboratory, we recently demonstrated the possibility o use LC-MS/MS analysis for the support of 2 microdosing trials.…”

Section: Discussionmentioning

confidence: 99%

Stable Isotopically Labeled Intravenous Microdose Pharmacokinetic Trials as a Tool to Assess Absolute Bioavailability: Feasibility and Paradigm to Apply for Protein Kinase Inhibitors in Oncology

Roosendaal

Rosing

Beijnen

2020

Clinical Pharm in Drug Dev

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“…In the last two decades, a series of important studies dealing with the dosage of ruxolitinib (among other tyrosine kinase inhibitors) in biological samples for pharmacokinetics and therapeutic drug monitoring evaluations were published [6][7][8][9][10]. In all these studies, highly performing procedures of sample treatment and quantitative analysis were developed and described in detail.…”

Section: Introductionmentioning

confidence: 99%

Improved Achiral and Chiral HPLC-UV Analysis of Ruxolitinib in Two Different Drug Formulations

et al. 2020

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In this paper, two new reversed-phase (RP) HPLC-UV methods enabling the quantitative achiral and chiral analysis of ruxolitinib in commercial tablets (containing 20 mg of active pharmaceutical ingredient, API) and not commercially available galenic capsules (with 5 mg of API) are described. For the achiral method based on the use of a water/acetonitrile [70:30, v/v; with 0.1% (v) formic acid] eluent, a “research validation” study was performed mostly following the “International Council for Harmonization” guidelines. All the system suitability parameters were within the acceptance criteria: tailing factor, between 1.7 and 2.0; retention factor, 2.2; number of theoretical plates, >9000. The linearity curve showed R2 = 0.99 (Rxv2 = 0.99), while trueness (expressed as recovery) was between 96.3 and 106.3%. Coefficient of variations (CVs) (repeatability: CVw and intermediate precision: CVIP) did not exceed 1.3% and 2.9%, respectively. Moreover, the use of the enantiomeric Whelk-O1 chiral stationary phases operated under similar RP eluent conditions as for the achiral analyses, and the “inverted chirality columns approach (ICCA)” allowed us to establish that the enantiomeric purity of ruxolitinib is retained upon reformulation from tablets to capsules. The two developed methods can allow accurate determinations of ruxolitinib in drug formulations for medical use.

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Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Cited by 30 publications

References 178 publications

Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC–MS/MS for application to a pharmacokinetic study in rats

Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC–MS/MS for application to a pharmacokinetic study in rats

Stable Isotopically Labeled Intravenous Microdose Pharmacokinetic Trials as a Tool to Assess Absolute Bioavailability: Feasibility and Paradigm to Apply for Protein Kinase Inhibitors in Oncology

Improved Achiral and Chiral HPLC-UV Analysis of Ruxolitinib in Two Different Drug Formulations

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