Simultaneous Determination of Formoterol Fumarate and Budesonide Epimers in Metered Dose Inhaler Using Ion-Pair Chromatography.

A simple, accurate and valid ion-pairing chromatographic method was developed for the simultaneous determination of formoterol fumarate (FF) and budesonide (BUD) epimers in metered dose inhaler. The separation was performed on C-18 column using mobile phase consisting of acetonitrile:0.05 M sodium acetate buffer (40:60% v/v) containing 0.03% sodium dodecyl sulfate adjusted to pH 3.1 using increasing volumes of either TEA or orthophosphoric acid isocratically eluted at 1.0 mL/min. Quantitation was achieved with UV detection at 214 nm. The retention times were 3.22, 6.41 and 6.91 min for formoterol fumarate, budesonide epimers B and A, respectively. The linearity range was 0.05-5.0 µg/mL for formoterol fumarate and 0.5-50.0 µg/mL for budesonide. The method was validated for, linearity; lower limit of quantification, lower limit of detection accuracy and precision. The proposed method is rapid (7 min), reproducible (RSD < 2.0%) and achieves satisfactory resolution between FF and BUD B (resolution factor = 12.07). The mean recoveries of the analytes in metered dose inhaler (99.97 and 99.83% for FF and BUD, respectively) were satisfactory.

Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity.

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric method (Method I) the absorbance was measured at 259 nm. The absorbance-concentration plot was rectilinear over the range 1.0-10.0 µg mL(-1) with a lower detection limit (LOD) of 0.078 µg mL(-1) and lower quantification limit (LOQ) of 0.238 µg mL(-1). Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II.

Simultaneous determination of labetalol and furosemide by first-derivative synchronous spectrofluorimetry.

A rapid, simple and highly sensitive first derivative synchronous spectrofluorimetric method was developed for the simultaneous analysis of a binary mixture of labetalol HCl (LBT) and furosemide (FUR) without prior separation. The method was based upon measuring the first derivative of synchronous fluorescence spectra of the two drugs at Deltalambda = 130 nm in aqueous ethanol (55% V/V). The different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully studied and optimized. The first derivative amplitude-concentration plots were rectilinear over the range of 0.10 to 1.00 microg/mL and 0.05-0.50 microg/mL with lower detection limits of 0.0149 and 7 x 10(-3) microg/mL and quantification limits of 0.045 and 0.021 microg/mL for LBT and FUR, respectively. The proposed method was successfully applied for the determination of the studied drugs in synthetic mixtures. The results obtained were in good agreement with those obtained by the reference methods.

Spectrophotometric determination of labetalol and lercanidipine in pure form and in pharmaceutical preparations using ferric-1,10-phenanthroline.

A simple and sensitive spectrophotometric method was developed for the determination of labetalol HCl (LBT) and lercanidipine HCl (LER) in pure form and in dosage forms. The method was based upon oxidation of the LBT and LER with Fe(+3) and the estimation of the produced Fe(+2) with 1,10-phenanthroline. The absorbance of the tris(1,10-phenanthroline) Fe(+2) complex was measured at 510 nm. Reaction conditions were optimized to obtain colored complex of higher sensitivity and longer stability. The absorbance concentration plots were rectilinear over the concentration rang of 5-90 and 1-20 µg/mL with lower detection limits of 0.74 and 0.01 µg/mL and quantification limits of 2.26 and 0.02 µg/mL for LBT and LER, respectively. The developed method was successfully applied for the determination of LBT and LER in bulk drugs and dosage forms. The common excipients and additives did not interfere in their determinations. There was no significant difference between the results obtained by the proposed and the reference methods regarding Student t-test and the variance ratio F-test.

Voltametric determination of vancomycin in dosage forms through treatment with nitrous acid.

Two methods are described for the determination of vancomycin (vancomycin hydrochloride, CAS 1404-93-9) in its dosage forms. The two methods involve a prior treatment with nitrous acid then measuring the formed nitroso derivative, either spectrophotometrically or polarographically. In the spectrophotometric method, the absorbance-concentration plot is rectilinear over the range of 4-32 micrograms/ml with minimum detectability of 2.7 micrograms/ml (1.8 x 10(-6) mol/l). The apparent molar absorptivity is 4.084 x 10(-4)l.mol-1.cm-1 and A (1%, 1 cm) is 275. The reaction product was also found to be polarographically reducible at the Dropping Mercury Electrode (DME) with E1/2 of-0.9 V vs. Ag/AgCl electrode and a diffusion current constant (Id) of 0.85 +/- 0.02. The cathodic current produced was found to be diffusion controlled with some adsorption contribution. The calibration plot was linear over the range of 0.015-0.06 mmol l-1 for direct current (DCt) mode and from 0.005-0.05 mmol l-1 for differential pulse polarography (DPP) mode with minimum detectability of 2.4 x 10(-7) mol l-1 using the latter technique. The results obtained were statistically compared with those given with the official B.P. method and were in good agreement.

Spectrofluorimetric determination of streptomycin in dosage forms and in spiked plasma using 9,10-phenanthraquinone.

A simple and highly sensitive method is proposed for the fluorimetric determination of streptomycin in dosage forms and in biological fluids. The method involves the reaction of streptomycin with 9,10-phenanthraquinone in alkaline medium to give a highly fluorescent derivative. The experimental parameters were carefully studied and incorporated into the procedures. The results obtained compared favourably with those obtained by the official methods. The concentration-fluorescence plots were rectilinear over the range 0.025-0.4 microg/ml, with minimum detectability (S/N=2) 0.006 microg/ml (4.19x10(-9) M). The proposed method was applied for the determination of streptomycin in dosage forms. The results obtained were in good agreement with those obtained by the official method. The proposed method was further applied to the determination of streptomycin in human plasma. The percentage recovery was 101.82. A proposal of the reaction pathway was presented.

Fluorimetric determination of some thioxanthene derivatives in dosage forms and biological fluids.

A simple and highly sensitive method is proposed for the fluorimetric determination of four thioxanthene derivatives, namely: chlorprothixene, clopenthixol, flupentixol and thiothixene, in dosage forms and biological fluids. The method involves the use of nitrous acid as an oxidant to produce the corresponding fluorescent thioxanthenone sulphoxides. The experimental parameters were carefully studied and incorporated into the procedures. The results obtained compare favourably with those obtained by the official methods. The concentration-fluorescence plots were rectilinear over the range of 0.04-0.4 microg/ml for thiothixene, and 0.02-0.25 microg/ml for the other compounds, with minimum detectability (S/N = 2) of 2 ng/ml for all the studied compounds except thiothixene which was 4 ng/ml. The proposed method was applied to the determination of the studied compounds in dosage forms. The results obtained were in good agreement with those obtained adopting the USP XIII method. The proposed method was further applied to the determination of flupentixol in spiked human urine and plasma, the percentage recoveries were 94.39 +/- 1.81 and 96.46 +/- 0.28, respectively. A proposal of the reaction pathway was presented.

Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms.

A kinetic spectrophotometric method has been developed for the determination of ampicillin (I) and amoxicillin (II). The method involves hydrolysis of the antibiotics with 1.0 M HCl, neutralization with 1.0 M NaOH followed by addition of palladium(II) chloride in the presence of 2 M KCl. The produced yellow colour is measured at 335 nm. The proposed method is valid over the concentration range 8-40 microg/ml and 10-40 microg/ml for I and II respectively with minimum detectability of 0.73 microg/ml and 0.76 microg/ml for I and II respectively. The determination of the studied compounds adopting the fixed concentration method is feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied to commercial dosage forms and the results obtained were in good agreement with those given by USP method.

Synthesis of certain new 2,4,5(6) trisubstituted-1,2,4-triazolo[1,5-alpha]pyrimidines as potential antihypertensive agents.

A series of 1,2,4-triazolol[1,5-alpha]pyrimidines bearing at position 2, morpholine, piperidine or piperazine moities has been prepared. In addition, ethyl 4-methyl-2-(4-acylpiperazin-1-yl)-1,2,4-triazolo[1, 5-alpha]pyrimidin-7(4H)-one-6-carboxylates 25,26, which have related structure with prazosin, have been synthesized. Ten representative compounds were tested in vitro and in vivo for their antihypertensive activity where compounds 7, 11 and 25 showed promising activity. The detailed synthesis, spectroscopic and biological data are reported.

Studies of complex formation between the bromophenol blue and some important aminoquinoline antimalarials.

A simple and rapid colorimetric method for the assay of amodiaquine hydrochloride, chloroquine phosphate and primaquine phosphate is described. The method is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex shows a maxima at 415-420 nm with high apparent molar absorptivities. Beer's law was obeyed in the concentration range 1-8, 2-10 and 2-12 micrograms.ml-1 for amodiaquine hydrochloride, primaquine phosphate and chloroquine phosphate respectively. The proposed method was applied to the determination of these drugs in certain formulations and the results were favourably comparable to the official methods.

Colorimetric and titrimetric assay of isoniazid.

Two methods are proposed for the determination of isoniazid in pure form or in tablets. In the first method chlorpromazine hydrochloride, when treated with 2-iodoxybenzoic acid as an oxidant in 50% w/v o-phosphoric acid solution, is oxidized to chlorpromazine free radical which absorbs at 530 nm. The red free radical is readily reduced quantitatively by isoniazid to the colourless chloropromazine. The addition of isoniazid to a red solution of chlorpromazine free radical results in a decrease in absorbance in direct proportion to the quantity of isoniazid. This forms the basis for the quantitative determination of micro-quantities of isoniazid (3-18 micrograms ml-1). The second method involves the titrimetric determination of isoniazid using N-bromophthalimide as a titrant. The end-point is determined either directly using methyl red or amaranth as indicator, or by a back titration method in which a known excess of N-bromophthalimide solution is added to isoniazid solution and then the residual unreacted reagent is determined iodometrically. The results by the proposed procedures were in good agreement with those obtained by the official methods.