Simultaneous determination of ergotamine, caffeine and dipyrone in their ternary mixture by applying double divisor and first derivative ratio spectra methods.

Two validated methods namely, double divisor ratio spectra derivative spectroscopy and derivative ratio spectroscopy with zero crossing point were applied to assay a ternary mixture of ergotamine tartrate (EGT), caffeine (CAF) and dipyrone sodium (DIP) without any additional separation steps. The linearity ranges using both methods were (1.0µg/mL-70.0µg/mL), (60.0µg/mL-100.0µg/mL) and (100.0µg/mL-300.0µg/mL) for EGT, CAF and DIP respectively. Double divisor ratio spectroscopy (method A) depends on dividing the different peak responses of EGT on (summation of peaks responses of CAF and DIP each of 10.0µg/mL concentration) at λ max=342nm, 310nm and 315nm for EGT, CAF and DIP respectively. Derivative ratio spectroscopy with zero crossing point (method B) depends on dividing the peak responses of two drugs (EGT and CAF) on (10.0µg/mL of DIP) and dividing the peak response of DIP on peak response of (10.0µg/mL of EGT). The detection limits of the studied drugs applying method A were (3.54, 12.96 and 8.748µg/mL), with quantitation limits of (10.73, 39.28 and 26.51µg/mL) for EGT, CAF and DIP respectively. Regarding method B, the limits of detection and quantitation for EGT were 0.604µg/mL and 1.829µg/mL respectively: with corresponding values of 19.44µg/mL and 58.92µg/mL for CAF and 20.44µg/mL and 61.9µg/mL for DIP. The obtained results were compared to those obtained by published methods and were found to be in accordance.

Second derivative synchronous fluorescence spectroscopy for the simultaneous determination of chlorzoxazone and Ibuprofen in pharmaceutical preparations and biological fluids.

A rapid, simple and highly sensitive second derivative synchronous fluorometric method has been developed for the simultaneous analysis of binary mixture of chlorzoxazone (CLZ) and ibuprofen (IP). The method is based upon measurement of the synchronous fluorescence intensity of these drugs at Δλ=60 nm in methanol. The different experimental parameters affecting the fluorescence of the two drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.2-4 µg/mL and 0.1-1.6 µg/mL for CLZ and IP, respectively with lower detection limits (LOD) of 0.028 and 8.3 × 10(-3) µg/mL and quantification limits (LOQ) of 0.086 and 0.03 µg/mL for CLZ and IP, respectively. The proposed method was successfully applied for the determination of the two compounds in synthetic mixtures and in commercial capsules. The high sensitivity attained by the proposed method allowed the determination of both drugs and real human plasma samples. The mean % recoveries in real human plasma (n=3) were 87.69 ± 6.15 and 92.57 ± 4.39 for each of CLZ and IP respectively.

Sensitive kinetic spectrophotometric determination of captopril and ethamsylate in pharmaceutical preparations and biological fluids.

A highly sensitive kinetic spectrophotometric method was developed for the determination of captopril (CPL) and ethamsylate (ESL) in pharmaceutical preparations and biological fluids. The method is based on a catalytic acceleration of the reaction between sodium azide and iodine in an aqueous solution. Concentration range of 0.1-1.5 microg ml(-1) for CPL and 0.3-3 microg ml(-1) for ESL was determined by measuring the decrease in the absorbance of iodine at 348 nm by a fixed time method. The decrease in absorbance after 5 min was markedly correlated to the concentration. The relative standard deviations obtained were 1.30 and 1.87 for CPL and ESL, respectively, in pure forms. Correlation coefficients were 0.9997 and 0.9999 for CPL and ESL, respectively. The detection limits were determined as (S/N = 3) were 20 ng ml(-1) for CPL and 50 ng ml(-1) for ESL. The proposed procedure was successively applied for the determination of both drugs in pharmaceutical preparations and in biological fluids.

Spectrophotometric determination of fenoterol hydrobromide in pure form and dosage forms.

A sensitive and rapid spectrophotometric procedure has been investigated for the determination of fenoterol either per se or in pharmaceutical preparations. The proposed procedure is based on the reaction between the drug and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) at pH 7.2, using borate buffer, to produce a yellow adduct. The latter has maximum absorbance at 400 nm and obeys Beer's law within the concentration range 5-30 microg/ml. Regression analysis of the calibration data showed a good correlation coefficient (r=0.9996) with minimum detection limit of 0.24 microg/ml (6.2 x 10(-8) M). The proposed procedure has been successfully applied to the determination of this drug in its tablets and in syrup, the mean percent recoveries were 97.45+/-0.59 and 98.7+/-0.64%, respectively. The results obtained are in good agreement with those given using a reference method. The pharmaceutical additives other than active ingredient did not interfere. A proposal of the reaction pathway has been postulated.

Spectrofluorometric determination of alpha-aminocephalosporins in biological fluids and pharmaceutical preparations.

A selective and highly sensitive fluorometric method was developed for the determination of four alpha-aminocephalosporins, namely cefaclor, cefadroxil, cephalexin and cephradine. The method involves the reaction of the target compounds with fluorescamine at a specific pH, ranging from 7.8 to 8.4. The produced derivatives exhibit maximum fluorescence intensities at 472-478 nm after excitation at 370-372 nm. The method is highly specific because other alpha-aminocephalosporins whose alpha amino group was blocked do not react similarly and hence do not interfere. At the specific pH range of the reaction where no degradation may occur with that medium the proposed method can be utilised as a stability-indicating assay. The different experimental parameters affecting the derivatisation reaction were carefully studied and incorporated into the procedure. Under the described conditions, the proposed method is linear over the concentration range of 0.05(-1) microg/ml(-1) for both cefaclor and cephalexin, and 0.05-0.65 and 0.025-0.5 microg/ml(-1) for cefadroxil and cepharadine, respectively and the coefficients of determination were greater than 0.999 (n = 3). The recoveries of the title compounds from spiked serum ranged from 88.6 to 89.7% and from spiked urine from 92.2 to 93.3% with a limit of quantitation (LOQ) of 25-50 ng/ml(-1) and limit of detection (LOD) of 5 ng/ml(-1) (S/N = 2) for all drugs. The mechanism of the fluorometric reaction is proposed and the advantages of the proposed method are discussed.

Estimation of the ionization pK(a) of pharmaceutical substances using the computer program Sparc.

The computer program sparc was used to calculate the pK(a) values of some important pharmaceutical substances. The sparc models proved to be suitable for estimating the pK(a) values of beta-adrenergic blocking agents and benzodiazepine drugs. Ionization macroconstants, microconstants, zwitterionic equilibria, speciation curves as a function of the pH and the isoelectric points of a semi-essential amino acid, arginine, and an anti-inflammatory, niflumic acid, were calculated.

Fluorimetric determination of aminoglycoside antibiotics using lanthanide probe ion spectroscopy.

The application of probe ion fluorimetry has succeeded in the microdetermination of six aminoglycoside antibiotics: neomycin, streptomycin, gentamicin, tobramycin, amikacin and kanamycin as sulfate salts in pure form and in some pharmaceutical preparations. The method is based on the reaction of Eu(3+) ions with aminoglycosides through amino and hydroxy groups. Such interactions enhance the intensity of the 616 nm fluorescence emission of the Eu(3+) ion. The fluorescence at 592 nm comes from a non-hypersensitive transition and is not affected by the ligand which is bound to the probe ions. The intensity ratio R, defined as I (592)I (616) was used to determine the amount of free and bound europium ions. A linear relationship between bound europium ions and aminoglycoside was found within the concentration ranges 20-100 ppm for neomycin, 5-60 ppm for streptomycin, and 10-70 ppm for gentamicin, tobramycin, amikacin, and kanamycin as sulfate salts. The percentage recoveries ranged from 99.22 to 101.07, with standard deviations ranging from +/- 1.5 to +/- 4.38. The relative stability constants ranged from 5 x 10(3) to 2 x 10(4). The optimum reaction conditions were studied and the results obtained compared favourably with the fluorimetric method using fluorescmine reagent.

Europium(III) ion probe spectrofluorometric determination of diclofenac sodium.

A new method has been devised for the determination of diclofenac sodium in bulk and in pharmaceutical preparations using Eu3+ ions as the Fluorescent probe. The technique was built around the hypersensitive property of the transitions of the fluorescent probe ion, Eu3+, at 616 nm. This is normally a forbidden transition, but the interaction with diclofenac sodium, which contains a carboxylic group, makes the transition allowed and enhances the intensity of its fluorescence emission. The Eu3+ fluorescence emission at 592 nm comes from a non-hypersensitive transition and is not affected by ligation. The intensity ratio, R, defined as I592/I616, was used as a measure of the percentage of bound probe ions. Diclofenac and Eu(III) forms a (1:1) molar complex. The relative stability constant of the complex was found to be 10(5). A linear relationship between bound Eu3+ and the concentration of diclofenac sodium was found for concentrations from 10 to 200 micrograms ml-1, with a recovery percentage of 100.22 +/- 2.27. The method shows a good agreement with a spectrophotometric method.

Sensitive colorimetric determination of copper (II) ions in some chemicals and multivitamins.

A sensitive and selective colorimetric method has been devised for the micro-determination of copper (II) ions in pure form, some chemicals and multivitamin preparations. The method depends on the formation of stable blue complexes in ammonia medium peaking at 615 nm between copper (II) ions, oxalyldihydrazide and one of the following aldehydes: 4-nitrobenzaldehyde, 2-nitrocinnamaldehyde and formaldehyde with minimum detection limits 0.1, 0.16 and 1.1 ppm, respectively. Several metal ions do not interfere. The optimum reaction conditions were studied and the results obtained were favorably comparable to the diethyldithiocarbamate method.