Spectrophotometric and atomic absorption spectrometric determination of ramipril and perindopril through ternary complex formation with eosin and Cu(II)

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of ramipril and perindopril. Both methods are based on the formation of a ternary complex, extractable with chloroform, between copper(II), eosin and the two cited drugs. Spectrophotometrically under the optimum condition, the ternary complexes showed an absorption maximum at 535 nm, with apparent molar absorptivities of 6.55 and 4.00×10³ mol⁻¹cm⁻¹ and Sandell’s sensitivities of 5.80×10⁻² and 1.04×10⁻¹μg cm⁻² for perindopril and ramipril, respectively. The solution of ternary complex obeyed Beer’s law in concentration ranges 10–60 and 20–100 μg ml⁻¹ for perindopril and ramipril, respectively. The proposed method was applied to the determination of the two cited drugs in pharmaceutical tablets. The atomic absorption spectrometric method, directly through the quantitative determination of copper content of the organic extract of the complex, was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and perindopril dosage forms.     

Spectrophotometric determination of enrofloxacin and pefloxacin through ion-pair complex formation

Two simple, quick and sensitive spectrophotometric methods are described for the determination of enrofloxacin and Pefloxacin. The methods are based on the reaction of these drugs with bromophenol blue (BPB) and methyl orange (MO) in buffered aqueous solution at pH 2.3-2.5 in case of bromophenol blue and at pH 3.6 with MO to give highly coloured complex species, extractable with chloroform. The coloured products are quantitated spectrophotometrically at 420 and 424 nm for BPB and MO, respectively. Optimisation of the different experimental conditions is described. Beer's law is obeyed in the concentration ranges 2-12 and 2-18 microg ml(-1) with BPB and in the ranges 1-12 and 4-40 microg ml(-1)with MO for enrofloxacin and pefloxacin, respectively. The proposed methods are applied for determination of Enroxil oral solution, Peflacine tablets and Peflacine ampoules with mean percentage accuracies 99.5+/-0.99, 99.39+/-1.05 and 100.02+/-0.895, respectively, with BPB and 100.30+/-0.89, 100.25+/-0.98 and 100.20+/-0.72, respectively, with MO.     

Spectrophotometric determination of nizatidine and ranitidine through charge transfer complex formation

Two Spectrophotometric procedures are presented for the determination of two commonly used H2-receptor antagonists, nizatidine (I) and ranitidine hydrochloride (II). The methods are based mainly on charge transfer complexation reaction of these drugs with either p-chloranilic acid (rho-CA) or 2, 3 dichloro-5, 6-dicyanoquinone (DDQ). The produced colored products are quantified spectrophotometrically at 515 and 467 nm in chloranilic acid and DDQ methods, respectively. The molar ratios for the reaction products and the optimum assay conditions were studied. The methods determine the cited drugs in concentration ranges of 20-200 and 20-160 microg/mL for nizatidine and ranges of 20-240 and 20-140 microg/mL for ranitidine with chloranilic acid and DDQ methods, respectively. A more detailed investigation of the complexes formed was made with respect to their composition, association constant, molar absorptivity and free energy change. The proposed procedures were successfully utilized in the determination of the drugs in pharmaceutical preparations. The standard addition method was applied by adding nizatidine and ranitidine to the previously analyzed tablets or capsules. The recovery of each drug was calculated by comparing the concentration obtained from the spiked mixtures with those of the pure drug. The results of analysis of commercial tablets and the recovery study (standard addition method) of the cited drugs suggested that there is no interference from any excipients, which are present in tablets or capsules. Statistical comparison of the results was performed with regard to accuracy and precision using student's t-test and F-ratio at 95% confidence level. There is no significant difference between the reported and proposed methods with regard to accuracy and precision.     

Spectrophotometric determination of gliclazide in pharmaceuticals and biological fluids through ternary complex formation with eosin and palladium (II)

A simple and sensitive spectrophotometric method has been developed for the determination of gliclazide (GLZ) in pharmaceutical formulations and biological fluids. The proposed method is based upon the formation of a ternary complex between palladium (II), eosin and GLZ in the presence of methyl cellulose as a surfactant and acetate buffer of pH 4.5. The ternary complex showed an absorption maximum at 550 nm. The solution of ternary complex obeyed Beer's law over the concentration range of 0.5-4 microg ml(-1) with minimum detectability (S/N = 2) of 0.05 microg ml(-1) (1.545 x 10(-7) M). The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. The proposed method was successfully applied to the analysis of commercial tablets. The results obtained were in good agreement with those obtained using the official or reference spectrophotometric method. The proposed method was further applied to spiked human urine and plasma, the percentage recoveries were 97.84 +/- 0.72 and 97.43 +/- 0.83, respectively, (n = 4). A proposal of the reaction pathway was presented.     

Spectrophotometric determination of flunarizine dihydrochloride through the formation of charge-transfer complex with iodine

A spectrophotometric method is described for the assay of flunarizine dihydrochloride. The method is based on the molecular interaction between the drug and iodine, to form a charge-transfer complex in which the drug acts as n-donor and iodine as σ-acceptor. The iodine was found to form charge-transfer complex in a 1:1 stoichiometry with absorption bands at 295 and 355 nm. The concentrations were linear over 8–13 μg ml⁻¹ at both 295 and 355 nm, respectively. A complete, detailed investigation of the formed complex was made with respect to its composition, associated constant and free energy change. The method has been applied successfully to the analysis of commercially available flunarizine dihydrochloride capsules without interference from the capsules excipient. To validate the proposed method, its accuracy and precision, the results were statistically compared with a newly developed reversed-phase HPLC procedure using Student-t and F-ratio tests.     

Spectrophotometric determination of ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation.

A spectrophotometric method was described for the determination of the antibacterial quinolone derivatives, ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation with three different acceptors. Chloranilic acid (CL) was utilized for their determination, forming charge transfer complex with lambdamax 520 nm. The proposed method was applied for determination of Ciprocin tablets, Enroxil oral solution, Peflacin ampoules and Peflacin tablets, with mean percentage accuracies, 99.58+/-1.25,99.94+/-0.96,100.91+/-1.59 and 99.86+/-1.003. Also, tetracyanoethylene (TCNE) was utilized in the determination of the concerned compounds forming charge transfer complexes with maximum absorbances at lambdamax 335 nm for ciprofloxacin and at lambdamax 290 nm for both enrofloxacin and pefloxacin. The procedure was applied for determination of Ciprocin tablets, Enroxil 10% oral solution, Peflacine tablets and Peflacine ampoules with mean percentage accuracies 99.40+/-1.27,99.95+/-0.90,98.98+/-1.565 and 99.88+/-0.998, respectively. Also, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was utilized for determination of pefloxacin forming charge transfer complex with maximum absorbance at lambdamax 460 nm. The procedure was applied for determination of peflacine tablets and peflacine ampoules with mean percentage accuracies 100.40+/-0.76 and 99.91+/-0.623, respectively. Statistical analysis of the obtained results showed no significant difference between the proposed method and other official and reported methods as evident from the t-test and variance ratio.     

Spectrophotometric and polarographic determination of enalapril and lisinopril using 2,4-dinitrofluorobenzene

The reaction of enalapril maleate and lisinopril with 2,4-dinitrofluorobenzene has been used to form colored products and polarographically active derivatives. The different experimental conditions have been optimized. The proposed methods have been validated and applied to the determination of both drugs in their commercial tablets. The results have been statistically compared with those obtained using the official HPLC methods.     

Spectrophotometric determination of some fluoroquinolone antibacterials by binary complex formation with xanthene dyes

Two simple, rapid and sensitive spectrophotometric methods for the determination of levofloxacin, norfloxacin and ciprofloxacin have been performed in pure form, pharmaceutical tablets and spiked human urine. Both methods are based on the formation of a binary complex between the drugs and one of the two xanthene dyes, eosin Y or merbromin in aqueous buffered medium. Under the optimum conditions, the binary complexes showed absorption maxima at 547 nm for eosin Y and 545 nm for merbromin. Using eosin Y, the calibration graph was linear over the range 2-8 microg ml(-1) for the three drugs with mean percentage recoveries 99.935 +/- 0.648, 99.973 +/- 0.678 and 100.011 +/- 0.606 for levofloxacin, norfloxacin and ciprofloxacin, respectively. While in case of merbromin, the concentration range was 2-15 microg ml(-1) with mean percentage recoveries 99.960 +/- 0.491, 100.017 +/- 0.510 and 99.980 +/- 0.506 for the three drugs, respectively. The proposed methods were successfully applied to determine these drugs in their tablet formulations and spiked human urine and the results compared favorably to that of reference methods. The suggested methods have the advantage of being applicable for the determination of the three drugs without prior extraction. They are recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical techniques are of great importance.     

Fluorimetric determination of some antibiotics in raw material and dosage forms through ternary complex formation with terbium (Tb(3+))

A highly sensitive and specific fluorimetric method was developed for the determination of cefazolin sodium I, cefoperazone sodium II, ceftriaxone sodium III, and cefixime IV. The proposed method involves the formation of ternary complex with Tb³⁺ in the presence of Tris buffer. The quenching of the terbium fluorescence due to the complex formation was quantitative for the four studied drugs. The effect of pH, concentration of Tris buffer and terbium were studied. The formation of the complex was highly dependent on the pH. The optimum pH was found to be pH 8 for cefazolin sodium I, ceftriaxone sodium III, cefixime IV and pH 10 for cefoperazone sodium II. The optimum concentration for Tb³⁺ was found 1 ml of 10⁻⁴ M solution and for Tris buffer 1 ml of the prepared solution. Under the described conditions, the proposed method was applicable over the concentration range 8.79×10⁻⁶–7.91×10⁻⁵, 9.7×10⁻⁶–4.49×10⁻5, 6.10×10⁻⁶–2.50×10⁻⁵, and 4.92×10⁻⁶–2.95×10⁻⁵ mol with mean percentage accuracy of 99.79±0.24, 98.97±1.25, 100.05±0.79, and 100.15±0.54 for I, II, III, and IV, respectively. The proposed method was applied successfully for the determination of studied drugs in bulk powder and in pharmaceutical formulations. The results obtained by applying the described method were statistically analyzed and compared with those obtained by applying the official method. The proposed method was used as stability indicating method for the determination of the studied drugs in the presence of their degradation products.     

Spectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe(III) ions

The formation of the complex between alendronate, non-chromophoric bisphosphonate drug important for the treatment of a variety of bone diseases, and iron(III) chloride in perchloric acid solution was studied. The stoichiometric ratio of alendronate to Fe(III) ions in the chromophoric complex was determined to be 1:1. The conditional stability constant was log K′_ave=4.50 (SD=0.15), indicating that the Fe(III)–alendronate complex is a complex of medium stability. The optimum conditions for this reaction were ascertained and a spectrophotometric method was developed for the determination of alendronate in the concentration range 8.1–162.5 μg ml⁻¹, the detection limit being 2 μg ml⁻¹. The method was validated for the direct determination of alendronate in tablet dosage formulations.     

Utilization of colorimetric and atomic absorption spectrometric determination of aztreonam through ion pair complex formation

Three rapid and sensitive, colorimetric and atomic absorption spectrometric methods were developed for the determination of aztreonam. The proposed methods depend upon the reaction of cobaltthiocyanate (I) or reineckate (II) ions with the drug to form stable ion-pair complexes which extractable with chloroform. The greenish blue and pink color complexes are determined either colorimetrically at lambda(max) 625 and 525 nm for I and II reagents, respectively, or by atomic absorption spectrometry, directly using the organic extracted complex, or indirectly, using the supernatant. The three procedures are applied for the determination of aztreonam in pure and in pharmaceutical dosage forms applying the standard additions technique and the results obtained agreed well with those obtained by the official method.     

Spectrophotometric determination of penicillamine and carbocisteine based on formation of metal complexes

A simple spectrophotometric method was developed for the determination of penicillamine and carbocisteine. The method depends on complexation of penicillamine with Ni, Co and Pb ions in acetate buffer pH of 6.3, 6.5 and 5.3, respectively, and carbocisteine with Cu and Ni ions in borate buffer pH of 6.7; 1-70 microg/ml of these drugs could be determined by measuring the absorbance of each complex at its specific lambdamax. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms. Also, the molar ratio and stability constant of the metal complexes were calculated and a proposal of the reaction pathway was postulated.     

Deoxyuridylate effects on thymidylate synthase-5-fluorodeoxyuridylate-folate ternary complex formation

The competitive basis and specificity of deoxyuridylate (dUMP)-mediated decreases in thymidylate synthase-5'-fluorodeoxyuridylate-folate (TS-FdUMP-folate) ternary complex formation at low concentrations of folates were investigated using charcoal isolation of protein-bound [3H]FuUMP ligand. Reaction conditions used 0.02 microM TS (Lactobacillus casei) and 0.10 microM [3H]FdUMP incubated for 10 min at 37 degrees and pH 7.4. Decreases in counts below control (C) values in dUMP-added samples (S) were expressed as C/S ratios. At CH2--H4PteGlu1 or H4PteGlu1 concentrations below 10 microM, highly linear relationships were found to exist between C/S value and dUMP concentrations, expressed as dUMP/FdUMP ratios. For H4PteGlu1, maximal C/S values for dUMP interference occurred at the lowest H4PteGlu1 concentrations, approaching the value of the TS-FdUMP binary complex. The efficiency of ternary complex formation by H4PteGlu1 was 28 +/- 5% of CH2--H4PteGlu1 values at concentrations below 1.0 microM. The protective effect of increasing H4PteGlu1 against dUMP interference resulted in a linear relationship between the logarithm of H4PteGlu1 concentration and the slope of dUMP interference (C/S vs dUMP/FdUMP). In contrast, the results with CH2--H4PteGlu1 were biphasic. At concentrations of CH2--H4PteGlu1 lower than 0.5 microM, C/S values were greater than those for binary complex alone, a result related to CH2--H4PteGlu1 consumption based on [5-3H]dUMP tritium-release studies. At concentrations of CH2--H4PteGlu1 above 1.0 microM, however, dUMP interference was nearly abolished. Kinetic analysis of the data suggests that this effect of the 5,10-methylene moiety may result in part from positive allosteric effects of first site TS-FdUMP-CH2--H4PteGlu1 ternary complex binding on acceleration of second site binding, in addition to slowed rates of dissociation. Other folylmonoglutamates showed relatively poor TS-[3H]FdUMP-folate complex formation: at 500 microM folate, as a percentage of CH2--H4PteGlu1 values, these were 29.6% for dihydrofolate, 7.5% for 5-CH3--H4PteGlu1, 3.0% for CH = H4PteGlu1, 1.6% for folic acid, 1.1% for 5-CHO--H4PteGlu1 (leucovorin) and 0.9% for 10-CHO--H4PteGlu1. Inhibitory effects by dUMP were consistent with binary complex effects alone for these folates. Study of methotrexate, as the monoglutamate and the hexaglutamate, suggested that ternary complexes with dUMP are favored over those with FdUMP at high concentrations of the antifolate. Our results indicate that activation of leucovorin to over 0.5 microM in intracellular CH2--H4PteGlu1 equivalents may be a requirement for achieving complete TS inhibition by FdUMP in the presence of excess conce     

Conductometric and indirect AAS determination of antimalarials

Two methods are described for the determination of amodiaquine hydrochloride, chloroquine phosphate and primaquine phosphate, based on the formation of their ion-associates with [Cd(2+), Co(2+), Mn(2+) and Zn(2+)] thiocyanate, ammonium reineckate and/or sodium cobaltinitrite. The molar combining ratio reveal that (1:1) (drug:reagent) ion associates are formed for all reagents except for ammonium reineckate which form (1:2) ion associates with all studied drugs. The optimum conditions for the ion-association have been studied. Conductometric method was applied for the direct determination of the suggested drugs in bulk powders, whereas indirect atomic absorption spectrometric method, depending on the measurement of the excess metal ion present in supernatant solutions after precipitation of the ion associates is used to calculate the drug concentration. Optimum concentration ranges for the determination of aminoquinoline antimalarial drugs under consideration were 0.46-12.90 and 0.155-3.87 mg using conductometric and indirect atomic absorption spectral methods, respectively. The proposed procedures have been applied successfully to the analysis of these drugs in certain formulations and the results are favourably comparable to the official methods.     

Spectrophotometric determination of some pharmaceutical amides through charge-transfer complexation reactions.

A spectrophotometric method is described for the assay of fenpipramide hydrochloride, isopropamide iodide, trimethobenzamide hydrochloride, morphazinamide hydrochloride and tolazamide. The method is based on the formation of a charge-transfer complex between the drug as n-donor and iodine, a sigma-acceptor. The product exhibits absorption maxima at 295 and 365 nm; measurements are made at 365 nm for fenpipramide and at 295 nm for the other compounds. Beer's law is obeyed in a concentration range of 1-120 micrograms ml-1. The method is rapid, simple and sensitive and can be applied to the analysis of some commercial and laboratory prepared tablets without interference. A more detailed investigation of the complex was made with respect to its composition, association constant and free energy change.     

Indirect determination of captopril by AAS

An indirect method is described for the determination of captopril (KPL) in pharmaceutical preparations by atomic absorption spectrometry (AAS). The procedure is based on the complexation of KPL with an excess of Pd(II) ion. The unreacted Pd(II) was resoluted on a cationic ion-exchanger resin, while Pd(II)-KPL sequestrate was not retained. The effluent Pd(II) sequestrade was measured by AAS. The absorbance is found to increase linearly with increasing KPL concentration, because the amount of Pd(II) is related to the concentration of KPL, which is corroborate by the calculated correlation coefficient value of 0.9939. The system obeys Beer's law for 1-40 microg ml(-1), S.D. was found to be 0.039 (n = 5). The Pd(II)-KPL complex was obtained in the solid phase. Characterization of the complex was performed by elemental analysis, TG, conductance measurements and IR, 1H-NMR spectroscopy.