Mahmoud A. Omar

Use of charge-transfer complexation in the spectrophotometric analysis of certain cephalosporins.

Three simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of cephapirin sodium (1), cefazoline sodium (2), cephalexin monohydrate (3), cefadroxil monohydrate (4), cefotaxime sodium (5), cefoperazone sodium (6) and ceftazidime pentahydrate (7) in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of these drugs as n-electron donors with the sigma-acceptor iodine, and the pi-acceptors: 2,3-dichloro-5,6-dicyano-p-benzo-quinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). Depending on the solvent polarity, different coloured charge-transfer complexes and radicals were developed. Different variables and parameters affecting the reactions were studied and optimized. The obtained charge-transfer complexes were measured at 364 nm for iodine (in 1,2-dichloroethane), 460 nm for DDQ (in methanol) and 843 nm for TCNQ (in acetonitrile). Ultraviolet-visible, infrared and (1)H-nuclear magnetic resonance techniques were used to study the formed complexes. Due to the rapid development of colours at ambient temperature, the obtained results were used on thin-layer chromatograms for the detection of the investigated drugs. Beers plots were obeyed in a general concentration range of 6-50, 40-300 and 4-24 mug ml(-1) with iodine, DDQ and TCNQ, respectively, with correlation coefficients not less than 0.9989. The proposed procedures could be applied successfully to the determination of the investigated drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 96.47 (+/-1.14) to 98.72 (+/-1.02) in the iodine method, 96.35 (+/-1.62) to 98.51 (+/-1.30) in the DDQ method, and 95.98 (+/-0.78) to 98.40 (+/-0.87) in the TCNQ method. The association constants and standard free energy changes using Benesi-Hildebrand plots were studied. The binding of cephalosporins to proteins in relation to their molar absorptivities was studied.

Kinetic spectrofluorimetric determination of certain cephalosporins in human plasma

An accurate, reliable, specific and sensitive kinetic spectrofluorimetric method was developed for the determination of seven cephalosporin antibiotics namely cefotaxime sodium, cephapirin sodium, cephradine dihydrate, cephalexin monohydrate, cefazoline sodium, ceftriaxone sodium and cefuroxime sodium. The method is based on their degradation under an alkaline condition producing fluorescent products. The factors affecting the degradation and the determination were studied and optimized. The reaction is followed spectrofluorimetrically by measuring the rate of change of fluorescence intensity at specified emission wavelength. The initial rate and fixed time methods were used for the construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 0.2-1.2 microg mL(-1) and 0.2-2.2 microg mL(-1) using the initial rate and fixed time methods, respectively. The results were statistically validated and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. The high sensitivity of the proposed method allows the determination of investigated cephalosporins in human plasma. The statistical comparisons of the results with the reference methods show an excellent agreement and indicate no significant difference in accuracy and precision.

Validated spectrofluorimetric method for determination of selected aminoglycosides

New, sensitive, and selective spectrofluorimetric method was developed for determination of three aminoglycoside drugs in different dosage forms, namely; neomycin sulfate (NEO), tobramycin (TOB) and kanamycin sulfate (KAN). The method is based on Hantzsch condensation reaction between the primary amino group of aminoglycosides with acetylacetone and formaldehyde in pH 2.7 yielding highly yellow fluorescent derivatives measured emission (471 nm) and excitation (410 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10-60, 40-100 and 5-50 ng/mL for NEO, TOB and KAN respectively. The proposed method was applied successfully for determination of these drugs in their pharmaceutical dosage forms.

Development of spectrofluorimetric method for determination of certain aminoglycoside drugs in dosage forms and human plasma through condensation with ninhydrin and phenyl acetaldehyde

A simple and sensitive spectrofluorimetric method has been developed and validated for determination of amikacin sulfate, neomycin sulfate and tobramycin in pure forms, pharmaceutical formulations and human plasma. The method was based on condensation reaction of cited drugs with ninhydrin and phenylacetaldehyde in buffered medium (pH 6) resulting in formation of fluorescent products which exhibit excitation and emission maxima at 395 and 470nm, respectively. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The calibration plots were constructed with good correlation coefficients (0.9993 for tobramycin and 0.9996 for both neomycin and amikacin). The proposed method was successfully applied for the analysis of cited drugs in dosage forms with high accuracy (98.33-101.7)±(0.80-1.26)%. The results show an excellent agreement with the reference method, indicating no significant difference in accuracy and precision. Due to its high sensitivity, the proposed method was applied successfully for determination of amikacin in real human plasma.

Kinetic spectrophotometric determination of certain cephalosporins in pharmaceutical formulations.

A simple, reliable, and sensitive kinetic spectrophotometric method was developed for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium, Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The method depends on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 610 nm. The initial rate and fixed time (at 3 minutes) methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 5–15 μg mL−1 and 5–25 μg mL−1 using the initial rate and fixed time methods, respectively. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. Statistical comparisons of the results with the reference methods show the excellent agreement and indicate no significant difference in accuracy and precision.

Enhancement of the sensitivity of valacyclovir and acyclovir for their spectrofluorimetric determination in human plasma

Two rapid, simple and highly sensitive spectrofluorimetric methods have been developed and validated for determination of valacyclovir hydrochloride (VAC) and acyclovir (ACV). The first method is based on measuring the intrinsic fluorescence of VAC or ACV in an aqueous acidic medium (pH 1.3) at 370 nm after excitation at 280 nm. The fluorescence intensity–concentration plots of VAC and ACV were rectilinear over the concentration ranges of 0.4–5.0 and 0.3–4.0 μg ml−1, respectively. The second method was based on the enhancement of the fluorescence intensity using sodium dodecyl sulfate (SDS) as a micellar system in an aqueous acidic medium (pH 1.3). This is the first attempt for enhancement of the sensitivity of these drugs by spectrofluorimetry. The addition of 2% w/v SDS, produced about 2.7 and 2.9 fold enhancements in the relative fluorescence intensity of VAC and ACV, respectively. The linear range for the second method was 0.2–2.5 and 0.1–1.25 μg ml−1, respectively. The proposed methods were successfully applied for determination of VAC and ACV in pharmaceutical preparations without interference from the common excipients. The high sensitivity of the micellar method permits its application for determination of ACV in human plasma with good percentage recovery.

Derivatization of labetalol hydrochloride for its spectrofluorimetric and spectrophotometric determination inhuman plasma: Application to stability study

Two simple, selective and accurate methods were developed for the determination of Labetalol hydrochloride in pure form and pharmaceutical tablets. Both methods are based on derivatization of the studied drug with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBDCl) in alkaline medium (pH7.5).The reaction product was measured spectrofluorimetrically at 540nm after excitation at 476nm (method I) or spectrophotometrically at 480nm (method II). The calibration graphs were rectilinear over the concentration ranges of 0.10-2.0 and 1.0-11.0μgmL-1 for methods I and II, respectively. The proposed methods were successfully applied to the analysis of commercial tablets without interference from common excipients. Furthermore, the spectrofluorimetric method was utilized for the in vitro determination of labetalol in spiked human plasma, with a percent mean recovery (n=3) of 97.80±1.29%. Moreover, the spectrofluorimetric method was extended to examine the stability study of LBT under different stress conditions such as alkaline, acidic, oxidative, photolytic and a thermal degradation.

Specific and highly sensitive spectrofluorimetric method for determination of febuxostat in its tablets and real human plasma. Application to stability studies

A simple, rapid, specific and highly sensitive spectrofluorimetric method has been developed for determination of febuxostat (FEB) in its tablets and real human plasma. The proposed method is based on the investigation of the fluorescence spectral behavior of FEB in an aqueous acidic system. The fluorescence intensity was measured at 400 nm after excitation at 335 nm. The fluorescence–concentration plot was rectilinear over the range 0.5–20.0 ng ml−1, with a limit of detection of 38.9 pg ml−1 and limit of quantification of 117.3 pg ml−1. The high sensitivity of the proposed method permits its application for the determination of FEB in real human plasma with good percentage recovery (81.73 ± 2.61). The application of the proposed method was further extended to stability studies of FEB after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines. A proposal for the degradation pathways was postulated.

Spectrofluorimetric determination of certain antidepressant drugs in human plasma

BackgroundCertain antidepressant drugs namely Sertraline hydrochloride, Fluoxetine hydrochloride, Paroxetine hydrochloride, Thioridazine hydrochloride and Amineptine hydrochloride were studied throughout this work using spectrofluorimetric method.MethodsThe spectrofluorimetric method is based on the charge-transfer reaction of these drugs as n-electron donors with 7,7,8,8-tetracyanoquinodimethane (TCNQ) as π-electron acceptor. The drug-TCNQ complexes showed excitation maxima ranged from 290-301 nm and emission maxima ranged from 443-460 nm.Results and discussionThe different experimental parameters affecting the formation and stability of the complexes were carefully studied and optimized. The calibration plots were constructed over the range of 50-450 ng mL-1 for Fluoxetine and Sertraline, 50-550 ng mL-1 for Paroxetine, 50-650 ng mL-1 for Thioridazine and 50-750 ng mL-1 for Amineptine. The proposed method was validated according to ICH and USP guidelines with respect to specificity, linearity, accuracy, precision and robustness.ConclusionA simple, reliable, sensitive and selective spectrofluorimetric method has been developed for determination of certain antidepressant. The proposed method was successfully applied to the analysis of the cited drugs in dosage forms. The high sensitivity of the proposed method allows determination of investigated drugs in spiked and real human plasma.

Development and validation of TLC–densitometric method for simultaneous determination of two binary antihypertensive mixtures containing felodipine in fixed dose combinations

A new densitometric thin-layer chromatographic method has been developed for simultaneous determination of two binary mixtures containing felodipine in combination with either metoprolol (mixture I) or ramipril (mixture II). The two mixtures were quantitatively separated on 60 F254 silica gel plates using toluene-ethyl acetate-methanol-ammonia as mobile phase with UV detection at 233 and 229 nm for mixtures I and II, respectively. The studied drugs were satisfactorily resolved with retention factor (Rf ) values of 0.34 ± 0.03 and 0.65 ± 0.03 for metoprolol and felodipine, respectively, in mixture I and 0.35 ± 0.03 and 0.74 ± 0.03 for ramipril and felodipine, respectively, in mixture II. Linearity ranges were 2000-7000 and 200-700 ng/band for metoprolol and felodipine, respectively, in mixture I and 1500-4000 ng/band for both ramipril and felodipine in mixture II. Correlation coefficient (r) values were 0.9968 for both metoprolol and felodipine in mixture I and 0.9993 for ramipril and 0.9989 for felodipine in mixture II. The method has been validated according to International Conference on Harmonization guidelines and has been successfully applied for determination of the studied drugs in their dosage forms without interference from commonly encountered excipients.