Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample processing and microbore liquid chromatography coupled with tandem mass spectrometry

Smith, Danielle; Tella, Max; Rahavendran, Sadayappan V.; Shen, Zhongzhou

doi:10.1016/j.jchromb.2011.08.009

Cited by 17 publications

(11 citation statements)

References 14 publications

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“…Nguyen et al reported a validated quantitative analysis for palbociclib in breast tumor homogenates using LC-MS/MS [8]. Smith et al introduced the use of an automated micro-sample processing for the pretreatment of mouse plasma samples prior to LC-MS/MS analysis of palbociclib; however, the availability of this system is restricted in many laboratories [9]. Recently, Paul et al described two bioanalytical methods for the quantification of palbociclib in rat plasma using an LC-MS method using a high-resolution quadrupole time of flight (Q-TOF) mass spectrometer, which is more convenient for qualitative rather than quantitative assays; therefore, the instrumentation is restricted in most bioanalytical laboratories [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

et al. 2019

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A novel method was developed and validated for the quantification of the three approved CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) in both human and mouse plasma and mouse tissue homogenates (liver, kidney, spleen, brain, and small intestine) using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). For all matrices, pretreatment was performed using 50 μL of sample by protein precipitation with acetonitrile, followed by dilution of the supernatant. Chromatographic separation of the analytes was done on a C18 column using gradient elution. A full validation was performed for human plasma, while a partial validation was executed for mouse plasma and mouse tissue homogenates. The method was linear in the calibration range from 2 to 200 ng/mL, with a correlation coefficient ( r ) ≥0.996 for each analyte. For both human and mouse plasma, the accuracy and precision were within ±15% and ≤15%, respectively, for all concentrations, except for the lower limit of quantification, where they were within ±20% and ≤20%, respectively. A fit-for-purpose strategy was followed for tissue homogenates, and the accuracy and precision were within ±20% and ≤20%, respectively, for all concentrations. Stability of all analytes in all matrices at different processing and storage conditions was tested; ribociclib and palbociclib were unstable in most tissue homogenates and conditions were modified to increase the stability. The method was successfully applied for the analysis of mouse samples from preclinical studies. A new ribociclib metabolite was detected in mouse plasma samples with the same m/z transition as the parent drug. Electronic supplementary material The online version of this article (10.1007/s00216-019-01932-w) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

et al. 2019

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“…It is difficult to compare our results with the clinical PK parameters of palbociclib as tumour concentrations as the mice bearing breast cancer xenografts for each measurement were treated with different palbociclib doses. In preclinical studies palbociclib intratumoural concentrations have been reported to be 25,163ng/gr (56.2μM) at 6 h after an oral dose of 100mg/kg, and plasma C max of 48ng/ml (0.11μM) after a dose of 2mg/kg (Nguyen et al, 2010;Smith et al, 2011). Human plasma C max from a palbociclib phase I study was 97.4ng/ml (0.21μM) in a multiple dose schedule, but again tumour palbociclib levels were not measured (Flaherty et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in whole blood palbociclib distributes preferentially into the cellular component over plasma, with a whole blood to plasma concentration ratio of 1.63 (EMA, 2016). Separate studies have reported plasma palbociclib PK (Smith et al, 2011) and intratumoural palbociclib concentrations in vivo (Nguyen et al, 2010) but were based on different doses and routes of administration.…”

Section: Introductionmentioning

confidence: 99%

Cellular Uptake and Efflux of Palbociclib In Vitro in Single Cell and Spheroid Models

Jové

Spencer

Hubbard

et al. 2019

J Pharmacol Exp Ther

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Adequate drug distribution through tumours is essential for treatment to be effective. Palbociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor approved for use in patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer (BC). It has unusual physicochemical properties, which may significantly influence its distribution in tumour tissue. We studied the penetration and distribution of palbociclib in vitro, including the use of multicellular three-dimensional models and mathematical modelling. MCF-7 and DLD-1 cell lines were grown as single cell suspensions (SCS) and spheroids; palbociclib uptake and efflux were studied using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Intracellular concentrations of palbociclib for MCF-7 SCS (C max 3.22µM) and spheroids (C max 2.91 µM) were 32 and 29 fold higher and in DLD-1, 13 and 7 fold higher, respectively than the media concentration (0.1 μM). Total palbociclib uptake was lower in DLD-1 cells than MCF-7 cells both in SCS and in spheroids. Both uptake and efflux of palbociclib were slower in spheroids than SCS. These data were used to develop a mathematical model of palbociclib transport that quantifies key parameters determining drug penetration and distribution. The model reproduced qualitatively most features of the experimental data and distinguished between SCS and spheroids, providing additional support for hypotheses derived from the experimental data. Mathematical modelling has the potential for translating in vitro data into clinically relevant estimates of tumour drug concentrations. Significance statement This study explores palbociclib uptake and efflux in single cell suspension and spheroid models of cancer. Large intracellular concentrations of palbociclib are found after drug exposure. The data from this study may aid understanding of the intratumoural pharmacokinetics of palbociclib which is useful in understanding how drug distributes within This article has not been copyedited and formatted. The final version may differ from this version.

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“…A literature survey revealed very few reports on LC–MS studies for the determination of PAL (Ma et al, ; Nguyen et al, ; Smith, Tella, Rahavendran, & Shen, ) or human pharmacokinetics. The sample preparation approaches in the above methods were tedious and time consuming.…”

Section: Introductionmentioning

confidence: 99%

“…A literature survey revealed very few reports on LC-MS studies for the determination of PAL (Ma et al, 2016;Nguyen et al, 2010;Smith, Tella, Rahavendran, & Shen, 2011) or human pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

An assessment of the impact of green tea extract on palbociclib pharmacokinetics using a validated UHPLC–QTOF–MS method

Paul

Surendran

Chandrakala

et al. 2019

Biomedical Chromatography

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Green tea extracts (GTE) has been reported to be a kinase inhibitor and modulator for various drug metabolizing enzymes. It may give synergetic antioncogenic effect, but with a possibility of pharmacokinetic interactions with various co‐administered anticancer agents like palbociclib (PAL), a selective inhibitor of CDK‐4/6 primarily metabolized by CYP3A enzyme. To explore the impact of GTE on PAL pharmacokinetics in Sprague–Dawley rats, a rapid and sensitive UHPLC–QTOF–MS method was established. Chromatographic separation was carried out on an Acquity UPLC BEH C18 (100 × 2.1 mm, 1.7 μm) column using a gradient mobile phase system consisting of 0.1% formic acid and acetonitrile. Sample preparation was based on a simple protein precipitation method. Estimation of target ions [M + H]+ at m/z 448.2455 for PAL and m/z 441.2044 for ibrutinib (IS) was performed in selective ion mode ESI–HRMS. Good sensitivity (1.0 ng/mL) and linearity over a wide concentration range of 1–2000 ng/mL was exhibited by the method. The results indicated that the administration of GTE resulted in decreased oral bioavailability of PAL in both short‐ and long‐term conditions. However, when both conditions were compared, the variation was less for the peak concentration and area under the concentration–time curve level of PAL.

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Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample processing and microbore liquid chromatography coupled with tandem mass spectrometry

Cited by 17 publications

References 14 publications

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

Cellular Uptake and Efflux of Palbociclib In Vitro in Single Cell and Spheroid Models

An assessment of the impact of green tea extract on palbociclib pharmacokinetics using a validated UHPLC–QTOF–MS method

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