Simultaneous quantitative determination of seven novel tyrosine kinase inhibitors in plasma by a validated UPLC-MS/MS method and its application to human microsomal metabolic stability study

Ezzeldin, Essam; Iqbal, Muzaffar; Herqash, Rashed N.; El-Nahhas, Toqa

doi:10.1016/j.jchromb.2019.121851

Cited by 38 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the drug’s registration, several analytical methods have been suggested to determine plasma ibrutinib concentrations [ 17 , 18 , 19 , 20 , 21 ]. However, the current work is the first to identify LSS facilitating whole plasma exposure determination and extending its implementation in routine clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

et al. 2021

View full text Add to dashboard Cite

Therapeutic drug monitoring of ibrutinib is based on the area under the curve of concentration vs. time (AUCIBRU) instead of trough concentration (Cmin,ss) because of a limited accumulation in plasma. Our objective was to identify a limited sampling strategy (LSS) to estimate AUCIBRU associated with Bayesian estimation. The actual AUCIBRU of 85 patients was determined by the Bayesian analysis of the full pharmacokinetic profile of ibrutinib concentrations (pre-dose T0 and 0.5, 1, 2, 4 and 6 h post-dose) and experimental AUCIBRU were derived considering combinations of one to four sampling times. The T0–1–2–4 design was the most accurate LSS (root-mean-square error RMSE = 11.0%), and three-point strategies removing the 1 h or 2 h points (RMSE = 22.7% and 14.5%, respectively) also showed good accuracy. The correlation between the actual AUCIBRU and Cmin,ss was poor (r2 = 0.25). The joint analysis of dihydrodiol-ibrutinib metabolite concentrations did not improve the predictive performance of AUCIBRU. These results were confirmed in a prospective validation cohort (n = 27 patients). At least three samples, within the pre-dose and 4 h post-dose period, are necessary to estimate ibrutinib exposure accurately.

show abstract

Section: Discussionmentioning

confidence: 99%

Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

et al. 2021

View full text Add to dashboard Cite

show abstract

“…34 We optimized the procedure and extended the range to 1-200 ng mL −1 , which was more applicable for the determination of afatinib in cell extracts. Two studies for the determination of osimertinib in human plasma used LLE or protein precipitation followed by evaporation to obtain a wide linear range of 5-1000 ng mL −1 and 1-1000 ng mL −1 , 14,18 respectively, compared with our range of 1-500 ng mL −1 in the cell extract. However, in contrast to our method, there was a slight ion suppression in the middle QC sample, and the precision of the absolute matrix effect in the low QC sample exceeded 15%.…”

Section: Discussionmentioning

confidence: 99%

“…An important criterion for the selection of the product ions was that there should be minimal MS interference on the MRM transitions, and these transitions were consistent with what had been observed in previous research. 14,15 Representative chromatograms of the blank matrix, blank matrix spiked with the IS and four analytes at LLOQ, and intracellular accumulation samples are presented in Figure 2. The retention times of anlotinib, osimertinib, afatinib, gefitinib and gefitinib-d8 (IS) were 1.7, 1.9, 1.7, 1.6 and 1.6 min, respectively.…”

Section: Application For Cellular Uptake Assaymentioning

confidence: 99%

“…A few LC/MS/MS methods have been developed to quantify anlotinib or TKIs in plasma, individually or in combination. [12][13][14][15] As anlotinib is a new TKI that was only approved in 2018, only two pharmacokinetic studies have described a sensitive method for anlotinib in plasma, with linear ranges of 0.1-20 and 0.1-50 ng mL −1 . 15,16 Reis et al reported a LC/MS/MS method to simultaneous quantify three EGFR TKIs (erlotinib, afatinib and osimertinib) in plasma, with a high lower limit of quantification (LLOQ) of 5 ng mL −1 and a long run time of 11 min.…”

Section: Introductionmentioning

confidence: 99%

“…16 Some studies have determined osimertinib or/and its metabolites in plasma by protein precipitation or liquid-liquid extraction (LLE) using an isocratic or a gradient mobile phase. 14,17 To the best of our knowledge, ours is the first method for the simultaneous determination of anlotinib and three generations of representative EGFR TKIs, especially in cellular matrices. Patel et al recently reported a method to determine three antiretroviral drugs in BMECs; however, the sample preparation procedure was complicated and time-consuming as it involved scraping cells, sample evaporation and reconstitution.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry

Zhou

et al. 2020

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Rationale Brain metastases are a common complication in patients with non‐small‐cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi‐target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared. Methods A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. Results The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2–200 ng mL−1 for anlotinib and gefitinib, 1–500 ng mL−1 for osimertinib and 1–200 ng mL−1 for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib. Conclusions A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.

show abstract

LC–MS/MS assay for the quantification of foretinib in rat plasma and its application to preclinical pharmacokinetic study

Guo

Zhang

Zhuang

et al. 2020

Biomedical Chromatography

View full text Add to dashboard Cite

A simple and sensitive ultra‐high‐performance liquid chromatography tandem mass spectrometric method was developed and validated for the determination of foretinib in rat plasma. The analyte and internal standard were extracted from the bio‐samples with acetonitrile and then separated on an Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) using 0.1% formic acid aqueous and acetonitrile as mobile phase, at a flow rate of 0.4 ml/min. The mass detection was performed in positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 317.1 > 128.1 for foretinib and m/z 502.2 > 323.1 for internal standard. The assay was demonstrated to be linear in the concentration range of 0.5–1000 ng/ml, with correlation coefficient >0.999. The mean extraction recovery of foretinib from rat plasma was within the range of 84.55–88.09%, while the matrix effect was in the range of 88.56–99.21%. The intra‐ and inter‐day precisions were <12.95% and the accuracy ranged from −7.55 to 8.57%. Foretinib was stable in rat plasma under the tested storage conditions. The validated assay was successfully applied to the pharmacokinetic study of foretinib in the rats. The results revealed that foretinib showed moderate elimination half‐life, low clearance and dose‐independent pharmacokinetic profiles inrats.

show abstract

Simultaneous quantitative determination of seven novel tyrosine kinase inhibitors in plasma by a validated UPLC-MS/MS method and its application to human microsomal metabolic stability study

Cited by 38 publications

References 34 publications

Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry

LC–MS/MS assay for the quantification of foretinib in rat plasma and its application to preclinical pharmacokinetic study

Contact Info

Product

Resources

About