&lt;p&gt;A New Validated HPLC-MS/MS Method for Quantification and Pharmacokinetic Evaluation of Dovitinib, a Multi-Kinase Inhibitor, in Mouse Plasma&lt;/p&gt;

AlRabiah, Haitham; Kadi, Adnan A.; Aljohar, Haya I.; Attwa, Mohamed W.; Al-Shakliah, Nasser S.; Attia, Sabry M.; Mostafa, Gamal A. E.

doi:10.2147/dddt.s223573

Cited by 4 publications

(6 citation statements)

References 18 publications

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“…The accuracy and precision of the proposed HPLC method in mouse plasma in the concentration range of 100–2000 ng/mL was examined [ 22 , 23 , 24 ]. Four quality control samples were analyzed for each concentration ( number of repation n = 3) during a single day and on different days.…”

Section: Resultsmentioning

confidence: 99%

“…Validation of the proposed HPLC-UV detection was examined according the US Food Drug and Administration guidelines [ 21 , 24 ]. The different criteria of validation parameters were assessed.…”

Section: Methodsmentioning

confidence: 99%

“…All animal experiments were conducted in accordance with the legal requirements in “Saudi Arabia for experiments with animals and humans”. The institutional review board of our university, as previously published [ 24 ], approved this study with the ethical approval No: SE-19-102.…”

Section: Methodsmentioning

confidence: 99%

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Development and Validation of an HPLC-UV Detection Assay for the Determination of Clonidine in Mouse Plasma and Its Application to a Pharmacokinetic Study

et al. 2020

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An accurate and simple HPLC-UV method has been developed for the determination of clonidine in mouse plasma. A reversed phase C18 Nova Pack® column (125 mm × 4.6 mm i.d., × 3 μm particle size) was used as stationary phase. The mobile phase composition was a mixture of 0.1% diethylamine/acetonitrile (70:30, v/v) at pH 8 in an isocratic mode at flow rate was 1.0 mL/min. Detection was set at 210 nm. Tizanidine was used as an internal standard. The clonidine and tizanidine were extracted from plasma matrix using the deproteinization technique. The developed method exhibited a linear calibration range 100.0–2000 ng/mL and the lower limit of detection (LOD) and quantification (LOQ) were 31.0 and 91.9 ng/mL, respectively. The intra-day and inter-day accuracy and precision of the method were within 8.0% and 3.0%, respectively, relative to the nominal concentration. The developed method was validated with respect to linearity, accuracy, precision, and selectivity according to the US Food and drug guideline. Minimal degradation was demonstrated during the determination of clonidine under different stability conditions. The suggested method has been successfully applied during a pharmacokinetic study of clonidine in mouse plasma.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Development and Validation of an HPLC-UV Detection Assay for the Determination of Clonidine in Mouse Plasma and Its Application to a Pharmacokinetic Study

et al. 2020

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“…The statistical method (least squared: y = ax + b) was used to calculate the calibration curve equation for RLC calibration levels. The LOD and LOQ were calculated as recommended by the Pharmacopeia using the intercept standard deviation (SD) and the calibration curve slope: 30,31 LOD ¼ 3:3 SD of intecept slope whereas LOQ ¼ 10 SD of intecept slope…”

Section: Methods Validationmentioning

confidence: 99%

LC–MS/MS Estimation of Rociletinib Levels in Human Liver Microsomes: Application to Metabolic Stability Estimation

Attwa¹,

Kadi²

2021

DDDT

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Background Rociletinib (CO-1686; RLC) is a new, small molecule that is orally administered to inhibit mutant-selective covalent inhibitor of most epidermal growth factor receptor (EGFR)-mutated forms, including T790M, L858R, and exon 19 deletions, but not exon 20 insertions. Non–small-cell lung cancer (NSCLC) with a gene mutation that encodes EGFR is sensitive to approved EGFR inhibitors, but usually resistance develops, which is frequently mediated by T790M EGFR mutation. RLC is an EGFR inhibitor found to be active in preclinical models of EGFR-mutated NSCLC with or without T790M. Methods In silico drug metabolism prediction of RLC was executed with the aid of the WhichP450 module (StarDrop software package) to verify its metabolic liability. Second, a fast, accurate, and competent LC-MS/MS assay was developed for RLC quantification to determine its metabolic stability. RLC and bosutinib (BOS) (internal standard; IS) were separated using an isocratic elution system with a C 18 column (reversed stationary phase). Results The developed LC-MS/MS analytical method showed linearity of 5–500 ng/mL with r 2 ≥ 0.9998 in the human liver microsomes (HLMs) matrix. A limit of quantification of 4.6 ng/mL revealed the sensitivity of the analytical method, while the acquired inter- and intra-day accuracy and precision values below 4.63% inferred the method reproducibility. RLC metabolic stability estimation was calculated using intrinsic clearance (20.15 µL/min/mg) and in vitro half-life (34.39 min) values. Conclusion RLC exhibited a moderate extraction ratio indicative of good bioavailability. The developed analytical method herein is the first LC-MS/MS assay for RLC metabolic stability.

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“…Fifty µL of internal standard WK3 (LTP) was then added to each concentration. The protein precipitation using organic solvent (ACN) was used for extraction of TEP and LTP [31][32][33]. Two ml of ACN was added to 1 mL of each calibration level and QC; they were vortex-mixed for 1 min and centrifuged at 14,000 rpm (at 4 • C for 12 min); then, the supernatant was filtered (0.22 µm syringe filter) into 1.5 mL HPLC vials, and 1 µL was injected into the LC-MS/MS instrument.…”

Section: Tep Calibration Standardsmentioning

confidence: 99%

An LC–MS/MS Analytical Method for Quantifying Tepotinib in Human Liver Microsomes: Application to In Vitro and In Silico Metabolic Stability Estimation

et al. 2023

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Tepotinib (MSC2156119) is a potent mesenchymal–epithelial transition (MET) factor inhibitor, a receptor tyrosine kinase that plays a crucial role in promoting cancer cell malignant progression. Adverse effects of tepotinib (TEP), such as peripheral edema, interstitial lung disease, nausea and diarrhea, occur due to drug accumulation and lead to termination of therapy. Therefore, the in silico and experimental metabolic susceptibility of TEP was investigated. In the current work, an LC-MS/MS analytical method was developed for TEP estimation with metabolic stability assessment. TEP and lapatinib (LTP) used as internal standards (ISs) were separated on a reversed-phase C18 column using the isocratic mobile phase. Protein precipitation steps were used to extract TEP from the human liver microsome (HLM) matrix. An electrospray ionization multi-reaction monitoring (MRM) acquisition was conducted at m/z 493→112 for TEP, at m/z 581→350, and 581→365 for the IS. Calibration was in the range of 5 to 500 ng/mL (R2 = 0.999). The limit of detection (LOD) was 0.4759 ng/mL, whereas the limit of quantification (LOQ) was 1.4421 ng/mL. The reproducibility of the developed analytical method (inter- and intra-day precision and accuracy) was within 4.39%. The metabolic stability of TEP in HLM was successfully assessed using the LC-MS/MS method. The metabolic stability assessment of TEP showed intermediate Clint (35.79 mL/min/kg) and a moderate in vitro t1/2 (22.65 min), proposing the good bioavailability and moderate extraction ratio of TEP. The in silico results revealed that the N-methyl piperidine group is the main reason of TEP metabolic lability. The in silico Star Drop software program could be used in an effective protocol to confirm and propose the practical in vitro metabolic experiments to spare resources and time, especially during the first stages for designing new drugs. The established analytical method is considered the first LC-MS/MS method for TEP estimation in the HLM matrix with its application to metabolic stability assessment.

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<p>A New Validated HPLC-MS/MS Method for Quantification and Pharmacokinetic Evaluation of Dovitinib, a Multi-Kinase Inhibitor, in Mouse Plasma</p>

Cited by 4 publications

References 18 publications

Development and Validation of an HPLC-UV Detection Assay for the Determination of Clonidine in Mouse Plasma and Its Application to a Pharmacokinetic Study

Development and Validation of an HPLC-UV Detection Assay for the Determination of Clonidine in Mouse Plasma and Its Application to a Pharmacokinetic Study

LC–MS/MS Estimation of Rociletinib Levels in Human Liver Microsomes: Application to Metabolic Stability Estimation

An LC–MS/MS Analytical Method for Quantifying Tepotinib in Human Liver Microsomes: Application to In Vitro and In Silico Metabolic Stability Estimation

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