Determination Of Imatinib Research Articles

Determination of imatinib as anticancer drug in serum and urine samples by electrochemical technique using a chitosan/graphene oxide modified electrode

The purpose of this work was to construct an electrochemical sensor for the detection of imatinib. It was based on a modified glassy carbon electrode (chitosan/rGO/GCE) that was a reduced graphene oxide nanocomposite. By employing a straightforward drop-casting technique, the rGO/chitosan composite was applied to the GCE surface. The XRD, FT-IR, and FE-SEM structural studies verified that graphene oxide was successfully reduced and that the rGO/chitosan nanocomposite was formed. The synergistic effect of rGO and chitosan boosted electron transfer kinetics and facilitated the oxidation reaction of imatinib on the electrode surface, according to electrochemical experiments, which indicated the chitosan/rGO/GCE's sensitive, selective, and stable response to imatinib. The findings showed sensitivity of 0.16502 μA/μM, detection limit value of 7.3 nM, and a wide and stable linear range of 1–300 µM. Differential pulse voltammetry measurements were performed on prepared human serum and urine samples to evaluate the applicability of chitosan/rGO/GCE for imatinib detection in real samples. For the prepared genuine samples, the chitosan/rGO/GCE showed good recoveries ranging from 95.00% to 99.20% with a relative standard deviation of 3.10–4.49%. These findings showed that imatinib in a variety of genuine samples may be accurately analyzed using the chitosan/rGO/GCE.

Fe3O4 nanoparticles decorated reduced graphene oxide&carbon nanotubes-based composite for sensitive detection of imatinib in plasma and urine

In this study, a new reduced graphene oxide (rGO) has been synthesized via a facile and envi­ronmentally friendly process using Callicarpa maingayi leaf extract. A novel magnetic catalyst based on Fe3O4 nanoparticles-reduced graphene oxide&carbon nanotubes ((Fe3O4--(rGO&CNT)) was prepared and characterized by hydrothermal method. The Fe3O4 nanoparticles with an average size of 25 to 40 nm were placed on carbon nanotubes and reduced graphene oxide sheets, while carbon nanotubes inserted between the reduced graphene oxide sheets effectively prevented their aggregation. The (Fe3O4-(rGO&CNT) composite has a large surface area and good electrocatalytic properties, suiting for the detection and determination of imatinib (IM) anticancer drug by voltammetry method. Under opti­mi­zed conditions, good linearity was achieved in the concentration range of 0.1 to 40 μmol L-1 and the limit of detection and sensitivity were 57 nmol L-1 and 3.365 μA L μmol-1, respectively. Furthermore, the fabricated sensor demonstrated acceptable reproducible behaviour and accuracy and a high level of stability during all electrochemical tests. In addition, the proposed method was applied for the detection of IM in biological samples and the recoveries were 94.0 to 98.5 %, with relative standard deviations of 2.1 to 4.4 %.

Application of Binary Metal-Organic Framework in an Electrochemical Sensor Decorated With Gold Nanoparticles for the Determination of Anticancer Drug Imatinib in Plasma

<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Imatinib mesylate is a receptor tyrosine kinase inhibitor drug with broad applications in cancer therapeutics, for example, in chronic myeloid leukemia and gastrointestinal stromal tumors. Due to its complications, the establishment of a monitoring technique for imatinib is necessary in clinical and environmental toxicology</i> . In this research, the electrochemical behavior of a modified carbon paste electrode by binary mixture of Ta/Cd MOF (metal-organic framework), which was electrochemically decorated with gold nanoparticles, has been investigated in the measurement of imatinib. The use of three metals in electrode structure makes the electron transition faster. The modified surface was studied using the microscopic and absorption method. The electrochemical performance of the modified electrode was evaluated by impedance, cyclic voltammetry and differential pulse voltammetry. The effective parameters in the sensitivity of the method were optimized. Quantitative measurements and determination of imatinib at the surface of the modified electrode were performed by using differential pulse voltammetry. Finally, the ability of the developed method to measure imatinib in real plasma samples was investigated. Under the optimal conditions, the linear range was obtained from 0.01 to 100 μM with a limit of detection of 3 nM. The repeatability of the method for the electrode to electrode (n=5) and one electrode (n=5) were 3.6 and 3.4%, respectively. The high efficiency of the developed electrode in plasma samples was proved by using high and acceptable accuracy and satisfactory relative recovery percentage (>91%). This electrochemical sensor also has excellent anti-interference performance.

VISIBLE SPECTROPHOTOMETRIC METHOD DEVELOPMENT AND VALIDATION OF IMATINIB IN BULK AND FORMULATION

Objective: A new, simple, sensitive, precise and reproducible UV visible spectrophotometric method was developed for the determination of Imatinib in pharmaceutical formulations with alizarin.&#x0D; Methods: The method is based on formation of yellow-colored complex. The UV spectrum of Imatinib in methanol showed λ max at 431 nm. Beer’s law is valid in the concentration range of 10-70 μg/ml. This method was validated for linearity, accuracy, precision, ruggedness and robustness.&#x0D; Results: The method has demonstrated excellent linearity over the range of 10-70 μg/ml with regression equation y =0.013x-0.017 and regression correlation coefficient r2= 0.997. Moreover, the method was found to be highly sensitive with LOD (4.3μg/ml) and LOQ (13.07μg/ml).&#x0D; Conclusion: Based on results the proposed method can be successfully applied for the assay of Imatinib in various pharmaceutical dosage forms.

In Situ Growth of Metal-Organic Framework HKUST-1 on Graphene Oxide Nanoribbons with High Electrochemical Sensing Performance in Imatinib Determination.

Metal-organic frameworks (MOFs) have been previously investigated as electrode materials for developing electrochemical sensors. They have usually been reported to suffer from poor conductivity and improvement in the conductivity of MOFs is still a great challenge. Here, we reported the fabrication of an electrochemical sensor based on the in situ growth of framework HKUST-1 on conductive graphene oxide nanoribbons (GONRs)-modified glassy carbon electrode (GCE) (HKUST-1/GONRs/GCE). The as-fabricated modified electrode was characterized using field emission scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, Fourier transform infrared, X-ray diffraction, electrochemical impedance spectroscopy, cyclic voltammetry, and Raman spectroscopy. The voltammetric response of HKUST-1/GONRs/GCE toward Imatinib (IMA), as an anticancer drug, is dramatically higher than HKUST-1/GCE because of the synergic effect of the GONRs and HKUST-1 framework. The calibration curve at the HKUST-1/GONRs/GCE for IMA covered two linear dynamic ranges, 0.04-1.0 and 1.0-80 μmol L-1, with a detection limit of 0.006 μmol L-1 (6 nmol L-1). Taking advantage of the conductivity of GONRs and large surface area of HKUST-1, a sensitive modified electrode was developed for the electrochemical determination of IMA. The present method provides an effective strategy to solve the poor conductivity of the MOFs. Finally, the obtained electrochemical performance made this modified electrode promising in the determination of IMA in urine and serum samples.

Determination of imatinib by liquid chromatography tandem mass spectrometry

Determination of imatinib by liquid chromatography tandem mass spectrometry

Determination of Imatinib and CGP74588 in Rat Plasma by HPLC and Its Application to a Pharmacokinetic Study

Determination of Imatinib and CGP74588 in Rat Plasma by HPLC and Its Application to a Pharmacokinetic Study

Validation of UV spectrophotometric and HPLC methods for quantitative determination of imatinib in bulk and pharmaceutical dosage form

Validation of UV spectrophotometric and HPLC methods for quantitative determination of imatinib in bulk and pharmaceutical dosage form

Magnetic solid-phase extraction of imatinib and doxorubicin as cytostatic drugs by Fe3O4/graphene oxide nanocomposite

Magnetic solid-phase extraction based on Fe3O4/graphene oxide nanocomposites was investigated for the separation, preconcentration and determination of imatinib and doxorubicin in aqueous solutions. Synthesis of Fe3O4/graphene oxide was characterized by transmission electron microscopy, energy-dispersive X-ray analyzer and vibrating sample magnetometer. After optimizing the conditions, optimal experimental conditions including sample pH, the amount of the magnetic nanoparticles, the effect of salt concentration and other chemotherapy medications, eluent type and extraction time were studied and established. The method showed good linearity for the determination of doxorubicin and imatinib in the concentration range of 0.01–100 μg mL−1 in aqueous solutions with limit of detection 1.8 ng mL−1 for doxorubicin and 1.9 ng mL−1 for imatinib. The relative recoveries of doxorubicin and imatinib levels were 96.7 and 88.4%, respectively. The results indicate that the present procedure is a suitable method for extraction of imatinib and doxorubicin from environmental water samples.

Development and Validation of a Stability Indicating RP-HPLC Method for the Determination of Imatinib Mesylate

The aim of this paper was to develop and validate the stability indicating RP-HPLC method for the determination of Imatinib mesylate in bulk and pharmaceutical dosage forms. A simple, accurate, precise, sensitive and stability indicating RP-HPLC method has been developed for the determination of Imatinib mesylate in bulk drug and pharmaceutical dosage form, in which separations are done using develosil C18, 5μm, 150 × 4.6mm i.d. column at a flow rate of 1.0mL/min with an injection volume of 20μL. The beer’s law was obeyed over the concentration range of 5 - 35μg/mL. The correlation coefficient was found to be 0.996 and it showed good linearity, reproducibility, precision in this concentration range. The % recovery values were found to be within the limits, which showed that the method was accurate. The LOD and LOQ were calculated using statistical methods. The % RSD values were less than 2. The developed method was successfully applied for determination of Imatinib mesylate in pharmaceutical dosage form. The results obtained are in good agreement with those obtained by using the standard method.

Biomass-based carbon dots: Synthesis and application in imatinib determination

Water-soluble carbon dots (CDs) have been synthesized by chemical oxidation treatment of the starch. The as-prepared CDs exhibit high fluorescence intensity, excitation-dependent photoluminescence behavior and bright blue fluorescence under ultraviolet lamp. Based on fluorescence quenching, a novel method for the determination of imatinib was developed with CDs. The linear relationship between the change of fluorescence intensity and the concentration of imatinib (10–400μgmL−1) was obtained with a relation coefficient of 0.9977. The recovery was in the range of 98.0–102.0% with a relative standard deviation of 1.5%, and the limit of detection was 2.4×10−3μgmL−1. The possible quenching mechanism between CDs and imatinib was found to be charge transfer.

Разработка и валидация методики количественного определения иматиниба в плазме крови методом высокоэффективной жидкостной хроматографии с масс-спектро- метрическим детектированием

Разработка и валидация методики количественного определения иматиниба в плазме крови методом высокоэффективной жидкостной хроматографии с масс-спектро- метрическим детектированием

Determination of Imatinib in the Blood Cells of Chronic Myelogenous Leukemia Patients by Ion-Trap Mass Spectrometry

Imatinib mesylate is a standard first-line therapy for patients with chronic myelogenous leukemia. However, there is still a significant proportion of these patients who reflect sub-optimal responses or fail imatinib therapy. Knowledge of the distribution within the studied system (e.g., peripheral blood) may be of high importance for understanding the principles of drug action and possible patient resistance to treatment. Intracellular or more precisely cell-associated, imatinib concentrations in patients, were shown to be higher compared to those in plasma, but still only limited data related to the methodology aspects of cell-associated concentrations are available. Herein is presented an assessment of the cell-associated imatinib determination assay by mass spectrometry. Three approaches were evaluated to isolate cells from the peripheral blood of chronic myelogenous leukemia patients. Erythrocyte lysis was found to cause substantial leakage of cell-associated imatinib in the first step. Selected alternative procedures utilizing density gradients did not affect the cell-associated imatinib concentration significantly. Cell isolates were subjected to flow cytometry which revealed differences in the population composition of peripheral blood cell isolates among individual patients indicating that the cell isolate composition should be addressed with the cell-associated imatinib concentration. The proposed approach may be utilized for the determination of intracellular concentration of imatinib and for other drugs in which the intracellular concentration plays a key role in the therapy.

Differential effects of ketoconazole, itraconazole and voriconazole on the pharmacokinetics of imatinib and its main metabolite GCP74588 in rat

The aim of the study was to develop a high performance liquid chromatography method for simultaneous determination of imatinib and CGP74588 in rat serum and study the inhibition effects of ketoconazole, itraconazole and voriconazole on pharmacokinetics of imatinib and CGP74588 in rats. In our study, we found that ketoconazole caused a significant increase (63.4%) in the AUC of imainib and a 28.8% increase in Cmax, which was greater than that of itraconazole but lower than that of voriconazole. When co-administered with voriconazole, pharmacokinetic parameters of imatinib were not significantly altered except for a 36.8% increase in the Cmax of imtinib. The Cmax of CGP74588 was decreased by 55.8% and AUC(0–∞) 49.7%, while the Vz/F and CLz/F values were increased by 1.7-fold and 1.1-fold, respectively. Itraconazole did not significantly influence the pharmacokinetic parameters of imatinib and CGP74588. The difference may be related to the different variation of inhibition sites of the three azole antifungal agents on CYP3A4 and P-gp. In clinical, when imatinib was co-administrated with ketoconazole or voriconazole, dose adjustment of imatinib should be taken into account.

Determination of imatinib and its active metabolite N-desmethyl imatinib in human plasma by liquid chromatography/tandem mass spectrometry

Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The pharmacokinetics of imatinib in patients with CML are characterised by large interpatient variability. Concentration monitoring of imatinib and its active metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe and effective use of imatinib. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry assay was developed for the simultaneous determination of imatinib and its metabolite DMI in human plasma. After proteins were precipitated with acetonitrile, imatinib, DMI and the internal standard D8-imatinib were resolved on a Gemini-NX 3 μm C18 column using gradient elution of 0.05 % formic acid and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves of imatinib and DMI were adequately fitted by quadratic equations (r > 0.999) over the concentration range of 10 to 2,000 ng/mL which encompasses clinical concentrations. Bias was ≤±8.3 %, intra- and inter-day coefficients of variation (imprecision) were ≤8.0 % and the limit of quantification was 10 ng/mL for both imatinib and DMI. The assay is being used successfully in clinical practice to enhance the safe and effective use of imatinib.

HPLC–MS/MS assay for the determination of imatinib and its metabolite CGP74588 concentrations in plasma

HPLC–MS/MS assay for the determination of imatinib and its metabolite CGP74588 concentrations in plasma

Liquid Chromatography‐Electrospray Mass Spectrometry Determination of Imatinib and Its Main Metabolite, N‐Desmethyl‐Imatinib in Human Plasma

The aim of this paper was to develop a specific and sensitive liquid chromatography/electrospray ionization mass spectrometry method for the determination of imatinib and its metabolite in human plasma. The method involved a solid phase extraction of the compounds and internal standard (imatinib‐D8) from human plasma. LC separation was performed on a SymmetryShield™ RP8 column with a mobile phase of water:acetonitrile:formic acid. MS data were acquired in single ion monitoring mode at m/z 494.4, m/z 480.4 and m/z 502.4 for imatinib, N‐desmethyl‐imatinib, and imatinib‐D8, respectively. The absence of ion suppression was demonstrated. The drug/internal standard peak area ratios were linked via a quadratic relationship to plasma concentrations (8.35–8350 µg/L for imatinib and N‐desmethyl‐imatinib). Precision was 2.8–10.8% and accuracy was 91.3–111.3%. Extraction recoveries were ≥70%. The lower limit of quantitation was 8.35 µg/L for both imatinib and N‐desmethyl‐imatinib.

Determination of imatinib (Gleevec ®) in human plasma by solid-phase extraction–liquid chromatography–ultraviolet absorbance detection

A sensitive HPLC method has been developed for the assay of imatinib in human plasma, by off-line solid-phase extraction followed by HPLC coupled with UV-Diode Array Detection. Plasma (750 μl), with clozapine added as internal standard, is diluted 3+1 with water and subjected to a solid-phase extraction on a C18 cartridge. After matrix components elimination with 2000 μl of water (in two aliquots of 1000 μl), imatinib is eluted with 3×500 μl MeOH. The resulting eluate is evaporated under nitrogen at room temperature and is reconstituted in 180 μl 50% methanol. A 50 μl volume is injected onto a Nucleosil 100–5 μm C18 AB column. Imatinib is analyzed using a gradient elution program with solvent mixture constituted of methanol and water containing both 0.05% ammonium acetate. Imatinib is detected by UV at 261 nm. The calibration curves are linear between 0.1 and 10 μg/ml. The limit of quantification and detection are 0.05 and 0.01 μg/ml, respectively. The mean absolute recovery of imatinib is 96%. The method is precise with mean inter-day CVs within 1.1–2.4%, and accurate (range of inter-day deviations −0.6 to +0.7%). The method has been validated and is currently being applied in a clinical study assessing the imatinib plasma concentration variability in a population of chronic myeloid leukemia- and gastro-intestinal stromal tumor-patients.