Indirect spectrophotometric determination of propranolol hydrochloride and piroxicam in pure and pharmaceutical formulations.

Two simple and sensitive indirect spectrophotometric methods for the assay of propranolol hydrochloride (PPH) and piroxicam (PX) in pure and pharmaceutical formulations have been proposed. The methods are based on the oxidation of PPH by a known excess of standard N-bromosuccinimide (NBS) and PX by ceric ammonium sulfate (CAS) in an acidic medium followed by the reaction of excess oxidant with promethazine hydrochloride (PMH) and methdilazine hydrochloride (MDH) to yield red-colored products. The absorbance values decreased linearly with increasing concentration of the drugs. The systems obeyed Beer's law over the concentration ranges of 0.5 - 12.5 and 0.3 - 16.0 microg/ml for PPH, and 0.4 - 7.5 and 0.2 - 10 microg/ml for PX with PMH and MDH, respectively. Molar absorptivity values, as calculated from Beer's law data, were found to be 1.36 x 10(4) and 2.55 x 10(4) l mol(-1) cm(-1) for PPH, and 2.08 x 10(4) and 2.05 x 10(4) l mol(-1) cm(-1) for PX with PMH and MDH, respectively. The common excipients and additives did not interfere with their determinations. The proposed methods have been successfully applied to the determinations of PPH and PX in various dosage forms. The results obtained by the proposed methods compare favorably with those of official methods.     

Indirect Spectrofluorimetric Determination of Piroxicam and Propranolol Hydrochloride in Bulk and Pharmaceutical Preparations

A simple and sensitive indirect spectrofluorimetric method for the assay of piroxicam (PX) and propranolol hydrochloride (PPH) in the pure form and in pharmaceutical formulations is proposed. This method is based on the oxidation of PX and PPH by a known excess of N-bromosuccinimide (NBS) followed by the reaction of the excess NBS with methdilazine hydrochloride (MDH) to yield fluorescent species. The fluorescence intensities were measured at 377 nm after excitation at 343 nm. The fluorescence intensities decrease linearly with an increase in concentration of PX and PPH over the ranges of 0.2–8.0 and 0.4–18.0 g/mL respectively. The common excipients and additives did not interfere in the determination. The proposed method has been successfully applied for the determination of PX and PPH in pharmaceutical formulations. The results have been validated by statistical data.     

Spectrophotometric Determination of Bio-Active Compounds in Commercial Samples with Nitrous Acid and Cresyl Fast Violet Acetate

Abstract

A simple and sensitive method for the spectrophotometric determination of bio-active compounds (drugs and non-nutritive sweeteners) containing reactive functional groups, viz., aromatic primary amine (drugs: Dapsone, Sulphamethoxazole), aromatic secondary amine (drug: Pindolol), aliphatic secondary amine (non-nutritive sweetener: Cyclamate), acid hydrazide (drug: Isoniazid) and thiol (drug: Captopril), is proposed. The method involves the addition of excess of sodium nitrite to the compound in the presence of 0.25 M hydrochloric acid solution and the unreacted nitrous acid is determined by the measurement of corresponding decrease in the absorbance of cresyl fast violet acetate (Δ_max : 555 nm), the most suitable one out of several dyes tested. This method was applied for the determination of bio-active compounds in commercial samples. (drugs: pharmaceutical formulations; non-nutritive sweetener (cyclamate): foodstuffs). The newly proposed method enabled the determination of the bio-active compounds in microgram quantities (0.1 - 0.5 μg/ml). Standard deviation values evaluated through replicate determinations were found to be < 0.5 mg per dose (RSD : 0.5 - 1.2%). The common excipients do not effect the determination of the drugs in pharmaceutical formulations. Many of the usually occurring additives in food stuffs are tolerated to a very high level in the determination of cyclamate in beverages, syrup, ice candy and ice cream. The validity of the method was tested against the reference method. Recoveries to the tune of 99.2 - 101.1% were observed by adopting this method.     

Spectrophotometric determination of H(2)-receptor antagonists via their oxidation with cerium(IV)

A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H(2)-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product (lambda(max) at 464nm). The decrease in the absorption intensity of the colored product (DeltaA), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990-0.9994) were found between DeltaA values and the concentrations of the drugs in a concentration range of 1-20microgml(-1). The assay limits of detection and quantitation were 0.18-0.60 and 0.54-1.53microgml(-1), respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3-102.6+/-0.57-1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.     

Simultaneous spectrophotometric determination of paracetamol and salicylamide in human serum and pharmaceutical formulations by a differential kinetic method

A rapid, simple, and sensitive differential kinetic method is presented for the determinations of acetaminophen (also known as paracetamol) and salicylamide. The method is based on their oxidation reaction by Fe3+ ion in the presence of 1, 10-phenanthroline as indicator. The reactions can be monitored spectrophotometrically by measuring the increase in the absorbance of the solution at 510 nm. Two times were selected one in which only paracetamol is oxidized by Fe3+ ion and the other in which both drugs are oxidized by Fe3+ ion. The data were evaluated by the proportional equations method. The method allowed the simultaneous determination of paracetamol and salicylamide at concentrations between 0.5-20 and 1-40 microg/mL with relative standard deviations of 3.47 and 2.58%, respectively. The method was applied to the simultaneous determination of paracetamol and salicylamide in human serum and pharmaceutical formulations.     

A sequential injection method for the determination of piroxicam in pharmaceutical formulations using europium sensitized fluorescence

A simple, selective and sensitive luminescence method for the assay of piroxicam (PX) in pharmaceutical formulation is developed. The method is based on the luminescence sensitization of europium (Eu³⁺) by complexation with PX. The signal for PX–EU is monitored at λ_ex=358 nm and λ_em=615 nm. Optimum conditions for the formation of the complex in methanol were 0.01 M TRIS buffer and 0.2 mM of Eu³⁺ which allows the determination of 100–2000 ppb of pX in batch method and 100–1000 ppb with limit of detection (LOD) = 23.0 ppb using sequential injection analysis (SIA). The relative standard deviations of the method range between 2 and 3% indicating excellent reproducibility of the method. The proposed method was successfully applied for he assay of PX in pharmaceutical formulations (Feldene capsules and tablets). Average recoveries of 101.0±0.3 and 98.8±2.7% were obtained for capsules in methanol using batch and sequential injection (SI) methods, respectively.     

Application of Pulsed Flow Analysis for Chemiluminescent Screening of Fluoxetine Counterfeit Pharmaceuticals

Abstract

A chemiluminometric methodology for fluoxetine determination based on its antioxidant scavenger effect on the fast chemiluminescence reaction between luminol and hypochlorite, is proposed. The developed procedure was implemented in a fully automated multi‐pumping flow system, combining the excellent mixing characteristics of the pulsed flow with chemiluminescence detection, resulting on a sensitive, simple, and fast procedure for fluoxetine determination in pharmaceutical formulations. Linear calibration plots for fluoxetine hydrochloride concentrations of up to 10 mg l^?1 (r=0.9995, n=7) were obtained, with an r.s.d<2% (n=10). Detection limit (3 σ) was 0.31 mg l^?1 and the sampling rate was about 136 determinations per h.     

Separation of p-xylene from multicomponent vapor mixtures using tubular MFI zeolite mmbranes

MFI zeolite membranes have been synthesized on tubular -alumina substrates to investigate the separation of p-xylene (PX) from m-xylene (MX) and o-xylene (OX) in binary, ternary, and simulated multicomponent mixtures in wide ranges of feed pressure and operating temperature. The results demonstrate that separation of PX from MX and OX through the MFI membranes relies primarily on shape-selectivity when the xylene sorption level in the zeolite is sufficiently low. For an eight-component mixture containing hydrogen, methane, benzene, toluene, ethylbenzene, PX, MX, and OX, a PX/(MX + OX) selectivity of 7.71 with a PX flux of 6.8 × 10⁻⁶ mol/(m² s) was obtained at 250 °C and atmospheric feed pressure. The addition of a small quantity of nonane to the multicomponent mixture caused drastic decreases in the fluxes of aromatic components and the PX separation factor because of the preferential adsorption of nonane in the zeolite channels. The nanoscale intercrystalline pores also caused serious decline in the PX separation factor. A new method of online membrane modification by carbonization of 1,3,5-triisopropylbenzene in the feed stream was found to be effective for reducing the intercrystalline pores and improving the PX separation.     

Automatic Multipumping Flow System for Handling Viscous Solutions: Application to the Spectrophotometric Determination of Trimipramine

Abstract

The present work describes the implementation, by using MultiPumping Flow Analysis System (MPFS), of a spectrophotometric method for the determination of trimipramine in commercially available pharmaceutical formulations, based on the reaction with ammonium monovanadate in acidic medium yielding a colored compound with a maximum of absorbance at 620 nm. The improved flow mixing conditions during sample and reagents insertion and transport, as a result of the chaotic movement of the solutions originated by the MPFS pulsed flow, assured a fast reaction zone homogenization in a reduced residence time, which was particularly advantageous for carrying out analytical determinations that involved highly viscous solutions, as is the case of the sulfuric acid solution used in the determination of trimipramine, without impairing the sampling rate.

A linear working range for trimipramine concentrations of up to 50 mg L^?1 (r = 0.9998; n = 6) was obtained, and the determined detection limit was about 1.15 mg L^?1. The sampling rate was approximately 50 determinations per hour. The obtained results were in agreement with those furnished by the reference procedure, with relative deviations lower than 4.7%. With the developed MPFS, the consumption of the reagents ammonium monovanadate and sulfuric acid was reduced by approximately 41.02% and 54.29%, respectively, compared with a previously proposed multicommutated flow analysis system.     

Gold electrodes from compact discs modified with platinum for amperometric determination of ascorbic acid in pharmaceutical formulations

A simple, rapid and precise amperometric method has been developed for quantification of ascorbic acid (AA) in pharmaceutical formulations using flow-injection analysis (FIA). A slice of recordable compact disc (CD) modified by electrodeposition of platinum was employed as the working electrode. The proposed flow system allows determinations in the 1 mumol l(-1) of the analyte and enables 90 determinations per h, employing only 150-mul sample. The method permits the direct quantification of ascorbic acid in many pharmaceutical products, avoiding cumbersome processes as previous separations, solvent extraction or sample filtration. This new procedure was applied to commercial pharmaceutical tablets and the results obtained were identical than the ones obtained by the classical iodometric method. The calibration plots for freshly prepared ascorbic acid standards were highly linear in the concentration range of 1-10 mumol l(-1) with a relative standard deviation (R.S.D.) <1%. For all real samples studied, the deviations were situated between 0.5 and 8.7%.     

A multicommutation-based flow system for multi-element analysis in pharmaceutical preparations

A flow system exploiting multicommutation and multidetection is proposed for sequential determinations in pharmaceutical preparations. The feasibilities were demonstrated by the determination of zinc, iron, copper, calcium and magnesium without changing the flow set-up. The gravitational flow of the solutions was exploited for addition of different chromogenic reagents and sample aliquots, thus avoiding the use of a propulsion unit. Transient signals at different wavelengths were measured simultaneously employing a fiber-optic multichannel spectrophotometer. Coefficients of variation of 1.0, 1.5, 1.4, 2.5 and 2.0% were obtained for iron, zinc, copper, calcium and magnesium, respectively. The mean sampling rate for the five species was 60 determinations per hour. In comparison to continuous reagent addition systems, the consumption was up to 160-fold lower. Results for pharmaceutical preparations agreed with those obtained by Flame atomic absorption spectrophotometry (FAAS) at the 95% confidence level.     

Development and Validation of LC Method for Simultaneous Determination of Two Binary Mixtures Containing Indapamide

A new sensitive, simple, rapid, and precise RP LC method with hydrochlorothiazide as internal standard has been developed for resolving two binary mixtures, perindopril with indapamide and captopril with indapamide, in pharmaceutical formulations. The drugs were separated at room temperature on a 250 mm × 4.6 mm, 5-μm particle, cyanopropyl column with 10 mm KH₂PO₄, pH 6.0-methanol 55:45 (v/v) as mobile phase at a flow rate of 1 mL min^?1. Detection was at 210 nm. Factors affecting the separation process were studied and optimized. The linearity, accuracy, and precision of the method were good, and the method was successfully applied to the determination of the two binary combinations in synthetic mixtures and commercial pharmaceutical products.     

Spectrophotometric investigations of the assay of physiologically active catecholamines in pharmaceutical formulations

Two simple, sensitive, and accurate spectrophotometric methods are proposed for the determination of levodopa (LD), methyldopa (MD), dopamine hydrochloride (DP), and pyrocatechol (PC) in pure and pharmaceutical preparations. The methods are based on measurement of the absorbances of tris(o-phenanthroline)iron(II) (method A) and tris(bipyridyl)iron(II) (method B) obtained by the oxidation of the catecholamines by iron(III) in the presence of 1,10-phenanthroline and 2,2'-bipyridyl at 510 and 522 nm, respectively. The absorbances were found to increase linearly with increases in the concentrations of the catecholamines, results which were corroborated by the calculated correlation coefficients (0.9990-0.9996). Beer's law was valid over the concentration ranges of 0.04-0.6, 0.06-0.75, 0.06-0.65, and 0.05-0.70 microg/mL in method A and 0.02-1.0, 0.04-1.3, 0.05-1.0, and 0.06-1.1 microg/mL in method B for PC, MD, LD, and DP, respectively. The common excipients and additives did not interfere in their determinations. The proposed methods were successfully applied to the assay of LD, MD, and DP in various dosage forms. The results were validated by statistical analysis.     

Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations

Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL(-1) for ciprofloxacin, 28.5-700 ng mL(-1) for enoxacin, 29.5-800 ng mL(-1) for norfloxacin and 33.5-1000 ng mL(-1) for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL(-1) for ciprofloxacin, 8.5 ng mL(-1) for enoxacin, 9.2 ng mL(-1) for norfloxacin and 9.98 ng mL(-1) for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method.     

Selective and stability-indicating methods for the simultaneous determination of mexiletine hydrochloride and/or its related substance: 2,6-dimethylphenol

Four simple, rapid, sensitive, and selective analytical procedures were developed for determination of mexiletine hydrochloride (MX) and/or its related substance: 2,6-dimethylphenol (DMP). The latter is a synthetic impurity for which a maximum pharmacopeial limit is defined. The first method depends on derivative-ratio spectrophotometry, for which the first-derivative signals of the ratio spectra at 259 nm (Deltalambda = 3 nm) are selected for the determination of MX. The second method is based on the spectrofluorometric measurement of MX in alkaline solution in the presence of 15 mM sodium dodecyl sulfate micellar medium at 292 nm (lambdaEx 260 nm). The third method is based on liquid chromatographic (LC) separation of MX and DMP on an RP-C8 column with a mobile phase consisting of 50 mM Na2HPO4-acetonitrile (60 + 40, adjusted to pH 2.4), and quantification of the analytes is achieved with UV detection at 212 nm based on peak area. The fourth method uses the coupling reaction of DMP with 2,6-dibromo-quinone-4-chlorimide (DBQC) in borate buffer to form an intensely colored product that was spectrophotometrically measured using first-derivative amplitudes at 670 nm (Deltalambda = 6 nm) for the determination of DMP. Different variables affecting each method were carefully investigated and optimized. The reliability and analytical performance of the proposed methods, including linearity, range, precision, accuracy, and detection and quantitation limits, were statistically validated. The first 3 methods were successfully applied for the stability-indicating determination of MX in laboratory-prepared mixtures with DMP, as well as for the determination of MX in capsules. Also, the LC and the DBQC spectrophotometric methods permitted the selective determination of DMP in the presence of a large excess of the parent drug at or near the pharmacopeial limit (0.1-1%).     

Validated Stability-Indicating HPLC–DAD Determination of the Antihypertensive Binary Mixture of Carvedilol and Hydrochlorothiazide in Tablet Dosage Forms

A simple and selective HPLC with diode array detection stability-indicating method was developed for the simultaneous determination of the antihypertensive drugs carvedilol (CRV) and hydrochlorothiazide (HCT) in their combined formulations. Effective chromatographic separation was achieved using Zorbax SB-C8 column (4.6 × 250 mm, 5 μm) with gradient elution of the mobile phase composed of 0.025 M phosphoric acid and acetonitrile at a flow rate of 1 mL min^?1. The multiple wavelength detector was set at 242 nm for measurement of CRV and 271 nm for HCT. Quantification was based on measuring the peak areas. The cited drugs were resolved with retention times 4.9 and 6.7 min for HCT and CRV, respectively. Analytical performance of the proposed HPLC procedure was thoroughly validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 5–300 and 5–200 μg mL^?1 for CRV and HCT, respectively, with correlation coefficients >0.9996. Both drugs were subjected to stress conditions of acidic and alkaline hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by resolution of the drugs from their forced degradation products. Moreover, specificity of the method was verified by resolution of both drugs from more than 20 pharmaceutical compounds of various medicinal categories. The validated HPLC method was applied to the analysis of the cited antihypertensive drugs in their combined tablet dosage forms. The proposed method made use of DAD as a tool for peak identity and purity confirmation.     

Spectrophotometric Determination of Cefadroxil in Drug Formulations using flow Injection Analysis

ABSTRACT

A flow injection analysis method for the determination of cefadroxil is proposed. The method is based on the hydrolysis of cefadroxil in sodium hydroxide solution followed by treatment with 1,4-phenylenediamine and Fe(III) in sulphuric acid solution to produce a violet color which has a maximum absorption at 600 nm. Variables such as acidity, reagent concentrations, flow rate of reagents and other FI parameters were optimized to produce the most sensitive and reproducible results. The calibration graph is linear between 80 - 320 mg/l. The detection limit is 40 mg/l with a relative standard deviation, RSD (n=6) of 1.8%. The proposed method, combining the advantages of speed and accuracy was applied to the determination of cefadroxil in pharmaceutical preparations. The results have been compared with those obtained using HPLC method (USP-procedure). Excellent agreement between the results of the proposed method and the HPLC method was observed.     

Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V)

Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at lambdamax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 microg mL-1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method.     

Ionic liquid sensitized fluorescence determination of four isoquinoline alkaloids

The fluorescence spectra of berberine, palmatine, jatrorrhizine, and coptisine in ionic liquids were studied and found to increase significantly in ionic liquids, with [C(8)MIM][PF(6)] having the greatest increase. Further studies showed that these drugs could be extracted from an aqueous solution by [C(8)MIM][PF(6)] using the temperature-assisted ionic liquid dispersive liquid phase microextraction method. The enrichment factors were 81.8-82.3, and the extraction recovery was 98.5%, 98.1%, 98.3%, and 98.8% for berberine, palmatine, jatrorrhizine, and coptisine, respectively. Based on the [C(8)MIM][PF(6)] preconcentration, separation, and sensitized fluorescence for these drugs, a new selective and sensitive method for the determination of concentration of these four drugs in aqueous samples was presented. At optimum conditions, the linear relationship was obtained in the ranges of 0.8-130 ng mL(-1), 0.9-160 ng mL(-1), 0.7-140 ng mL(-1), and 0.6-110 ng mL(-1), respectively. The proposed method was successfully applied for the determination of the drugs in pharmaceutical preparations, urine, and plasma samples.     

Simultaneous Determination of Tranexamic Acid and Losartan Potassium in Dosage Formulations and Human Serum by RP-LC

Rapid liquid chromatographic procedure for analytical quality control of pharmaceutical preparations and human serum containing drugs, tranexamic acid together with losartan potassium are proposed, using acetonitrile: water (50:50), adjusting pH to 2.6 with phosphoric acid as a mobile phase, UV detection at 205 nm and propylparaben sodium was used as internal standard. The results obtained showed a good agreement with the declared contents. The method shows good linearity in the range of 40–10,000 ng mL^?1 for tranexamic acid serum concentrations with a correlation coefficient 0.9999 (inter- and intra-day CV <3.18) and in the range 5–10,000 ng mL^?1 for losartan potassium serum concentrations with a correlation coefficient 0.9999 (inter- and intra-day CV <3.61). The recovery was >97.8%. The proposed method may be used for the quantitative analysis of tranexamic acid and losartan potassium alone or in combination from raw materials, in bulk drugs, dosage formulations and in serum.