Spectrophotometric and computational investigations of charge transfer complexes of chloranilic acid with tyrosine kinase inhibitors and application to development of novel universal 96-microwell assay for their determination in pharmaceutical formulations

The tyrosine kinase inhibitors (TKIs) are chemotherapeutic drugs used for the targeted therapy of various types of cancer. This work discusses the experimental and computational evaluation of chloranilic acid (CLA) as a universal chromogenic reagent for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for TKIs. The reaction resulted in an instantaneous formation of intensely purple colored products with TKIs. Spectrophotometric results confirmed that the reactions proceeded via the formation of charge-transfer complexes (CTCs). The physical parameters were determined for the CTCs of all TKIs. Computational calculations and molecular modelling for the CTCs were conducted, and the site(s) of interaction on each TKI molecule were determined. Under the optimized conditions, Beer’s law correlating the absorbances of the CTCs with the concentrations of TKIs were obeyed in the range of 10–500 µg/well with good correlation coefficients (0.9993–0.9998). The proposed MW-SPA fully validated and successfully applied for the determination of all TKIs in their bulk forms and pharmaceutical formulations (tablets). The proposed MW-SPA is the first assay that can analyze all the TKIs on a single assay system without modifications in the detection wavelength. The advantages of the proposed MW-SPA are simple, economic and, more importantly, have high throughput.

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Spectrophotometric Analysis of Selective Serotonin Reuptake Inhibitors Based on Formation of Charge-Transfer Complexes with Tetracyanoquinodimethane and Chloranilic Acid

Journal of AOAC International ◽

10.1093/jaoac/89.2.326 ◽

2006 ◽

Vol 89 (2) ◽

pp. 326-333 ◽

Cited By ~ 18

Author(s):

Ibrahim A Darwish ◽

Ibrahim H Refaat

Keyword(s):

Charge Transfer ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Pharmaceutical Formulations ◽

Spectrophotometric Analysis ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Charge Transfer Complexes ◽

Chloranilic Acid ◽

Relative Standard

Abstract A simple, accurate, and sensitive spectrophotometric method for analysis of selective serotonin reuptake inhibitors (SSRIs) has been developed and validated. The analysis was based on the formation of colored charge-transfer complexes between the intact molecule of SSRI drug as an n-electron donor and each of tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (pCA) as electron acceptors. The formed complexes were measured spectrophotometrically at 842 and 520 nm for TCNQ and pCA, respectively. Different variables and parameters affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.99750.9996) were found between the absorbances and the concentrations of the investigated drugs in the concentration ranges of 450 and 20400 g/mL with TCNQ and pCA, respectively. With all the investigated drugs, TCNQ gave more sensitive assays than pCA; the limits of assay detection were 2.54.8 and 2040 g/mLwith TCNQ and pCA, respectively. The intra- and interassay precisions were satisfactory; the relative standard deviations did not exceed 2. The proposed procedures were successfully applied to the analysis of the studied drugs in pure form and pharmaceutical formulations with good accuracy; the recovery values were 98.4102.8 1.241.81. The results obtained from the proposed method were statistically comparable with those obtained from the previously reported methods.

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CHEMOMETRICS ASSISTED RP-HPLC METHOD DEVELOPMENT FOR THE SEPARATION OF SECOND GENERATION TYROSINE KINASE INHIBITORS IN BULK DRUGS AND PHARMACEUTICAL FORMULATIONS M Rajavardhan Reddy, Kirtimaya Mishra, P.K.Manna, R Suresh * DOI: 10.7897/2230-8407.09112

International Research Journal of Pharmacy ◽

10.7897/2230-8407.09112 ◽

2018 ◽

Vol 9 (1) ◽

pp. 81-88

Author(s):

M Rajavardhan Reddy ◽

Kirtimaya Mishra ◽

P K Manna ◽

R Suresh

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Method Development ◽

Second Generation ◽

Kinase Inhibitors ◽

Pharmaceutical Formulations ◽

Hplc Method ◽

Rp Hplc ◽

Hplc Method Development

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Use of the Charge Transfer Reactions for the Spectrophotometric Determination of Risperidone in Pure and in Dosage Forms

Journal of Pharmaceutics ◽

10.1155/2013/792186 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6

Author(s):

Hemavathi Nagaraju Deepakumari ◽

Hosakere Doddarevanna Revanasiddappa

Keyword(s):

Charge Transfer ◽

Pharmaceutical Preparations ◽

Pharmaceutical Formulations ◽

Molar Absorptivity ◽

Charge Transfer Complexes ◽

Chloranilic Acid ◽

Colored Complex ◽

Relative Standard ◽

Complexation Reactions

The aim of study was to develop and validate two simple, sensitive, and extraction-free spectrophotometric methods for the estimation of risperidone in both pure and pharmaceutical preparations. They are based on the charge transfer complexation reactions between risperidone (RSP) as n-electron donor and p-chloranilic acid (p-CA) in method A and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in method B as π-acceptors. In method A, RSP reacts with p-CA in methanol to produce a bright pink-colored chromogen measured at 530 nm whereas, in method B, RSP reacts with DDQ in dichloromethane to form orange-colored complex with a maximum absorption at 460 nm. Beer's law was obeyed in the concentration range of 0–25 and 0–50 μg/mL with molar absorptivity of and L/moL/cm for RSP in methods A and B, respectively. The effects of variables such as reagents, time, and stability of the charge transfer complexes were investigated to optimize the procedures. The proposed methods have been successfully applied to the determination of RSP in pharmaceutical formulations. Results indicate that the methods are accurate, precise, and reproducible (relative standard deviation %).

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