Sensitive Spectrophotometric Determination of Some Dibenzazepine Drugs with Diazotized P-Phenylenediamine Dihydrochloride

ABSTRACT

A simple, sensitive and selective spectrophotometric procedure was developed for the determination of imipramine hydrochloride, desipramine hydrochloride, clomipramine hydrochloride and trimipramine maleate belonging to dibenzazepine class of drugs. The method is based on the interaction of diazotized p-phenylenediamine dihydrochloride with the drug in sulphuric acid medium. The resulting chromophore was measured at 565 nm, and was stable for about 2.5 hr. The commonly encountered excipients and additives do not interfere with the determination. Dibenzazepine drugs can be determined in the range of 0.1-4.0 μg/ml, with a relative standard deviation of 1.92% for ten replicate measurement of 2.0 μg/ml dibenzazepine drugs. Results from the analysis of preformulations and commercial tablets by this procedure agree well with those of the official method.     

Charge-transfer complexes of phenylephrine with nitrobenzene derivatives

The molecular charge-transfer complexes of phenylephrine with picric acid and m-dinitrobenzene have been studied and investigated by IR, 1H NMR electronic spectra in organic solvents and buffer solutions, respectively. Simple and selective methods are proposed for the determination of phenylephrine hydrochloride in bulk form and in tablets. The two methods are based on the formation of charge-transfer complexes between drug base as a n-donor (D) and picric acid, m-dinitrobenzene as pi-acceptor (A). The products exhibit absorption maxima at 497 and 560 nm in acetonitrile for picric acid and m-dinitrobenzene, respectively. The coloured product exhibits an absorption maximum at 650 nm in dioxane. The sensitive kinetic methods for the determination phynylephrine hydrochloride are described. The method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time at 20 min.     

Spectrophotometric determination of nicoumalone, acebutolol hydrochloride and procainamide hydrochloride

A sensitive spectrophotometric method is described for the determination of nicoumalone (NIC), acebutolol hydrochloride (ACBH) or procainamide hydrochloride (PAH) either in pure form or in pharmaceutical formulations. The method is based on the oxidative coupling reaction through the involvement of an aromatic primary amino group (released through reduction in NIC or hydrolysis in ACBH or existing free in PAH) in the drug with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of ferric chloride [Fe(III)]. The resulting chromophores are measured at 620 nm for NIC and ACBH and 580 nm for PAH. The concentration measurements are reproducible within a relative standard deviation of 1%.     

Spectrophotometric methods for the determination of prazosin hydrochloride in tablets

Four simple and sensitive methods for the assay of prazosin hydrochloride (PRH) are developed. These methods are based on the formation of coloured species by treating it either with excess N-bromosuccinimide (NBS) and determining the unconsumed NBS with p-N-methyl aminophenol sulphate (metol)-sulphanilamide (SA) reagent (method A, lambda(max) 520 nm): with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of eerie ammonium sulphate (CAS) (method B, lambda(max) 620 nm) or with acidic dyes such as orange-II (O-II) (method C, lambda(max) 490 nm) and alizarin violet 3B (AV-3B) (method D, lambda(max) 570 nm) under the specified experimental conditions. Regression analysis of Beer's law plot showed good correlation in the concentration range of 1.0-10.0, 2.5-25.0, 1.0-17.5 and 2.5-30.0 mug ml for methods A, B, C and D respectively.     

Spectrophotometric Determination of Aminoglutethimide by Diazotization and Subsequent Coupling

Abstract

Three simple and sensitive spectrophotometric methods for the determination of aminoglutethimide are described. The first method is based on the diazotization of the drug and the reaction product is quantified spectrophotometrically at 273 nm. The second and third methods involve coupling of the diazotized salt of the drug with either ethyl acetoacetate (EAA) in alkaline medium or N-(1-naphthyl)ethylenediamine hydrochloride (NED) in acid medium, to give colored reaction products measurable at 368 nm and 558 nm, respectively. The optimization of different experimental conditions is described. The proposed methods were applied successfully to the determination of amino-glutethimide in tablets with good accuracy and precision. The reliability of the developed methods were established by comparing the obtained results with those given by the official United States Pharmacopeial XXII methods.     

New and Sensitive Method for the Spectrophotometric Determination of Certain Tricyclic Antidepressants

 A new, simple, and sensitive spectrophotometric method for the determination of certain tricyclic antidepressants, belonging to the dibenzazepine class of drugs, has been developed. The proposed method is based on the reaction of imipramine hydrochloride (IPH), desipramine hydrochloride (DPH), clomipramine hydrochloride (CPH), trimipramine maleate (TPM) or opipramol (OPP) with iron(III), and subsequent reaction with ferricyanide in an acetic acid medium, to yield a blue product, with maximum absorption at 720–730 nm. Received January 24, 2000     

Development and validation of LC methods with visible detection using pre-column derivatization and mass detection for the assay of voglibose

Two sensitive and selective liquid chromatographic methods were developed for the assay of voglibose (VB) and validated as per International Conference on Harmonization (ICH) guidelines. First method is based on the pre-column derivatization of VB followed by visible detection (LC-VD) and second method involves mass spectrometric detection (LC-MS). In LC-VD method, VB was derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was run through Novapak C18 (300 × 3.9 mm, 4 μm) column using the mobile phase containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio. The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in LC-VD method is described. DCPVB structure was confirmed by mass spectral analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 × 4.6 mm, 5 μm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as mobile phase. The assay concentrations of VB in pure form and in tablets for LC-VD and LC-MS methods are 25 and 5 ng ml⁻¹, respectively.     

Quantitative analysis of rabeprazole sodium in commercial dosage forms by spectrophotometry

The main aim of this work is to develop and validate two spectrophotometric methods for the quantitative analysis of rabeprazole sodium in commercial dosage forms. Method A is based on the reaction of drug with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of ammonium cerium(IV) nitrate in acetic acid medium at room temperature to form red-brown product which absorbs maximally at 470 nm. Method B utilizes the reaction of rabeprazole sodium with 1-chloro-2,4-dinitrobenzene (CDNB) in dimethyl sulfoxide (DMSO) at 45+/-1 degrees C to form yellow colored Meisenheimer complex. The colored complex has a characteristic band peaking at 420 nm. Under the optimized reaction conditions, proposed methods are validated as per ICH guidelines. Beer's law is obeyed in the concentration ranges of 14-140 and 7.5-165 microg ml(-1) with linear regression equations of A=6.041 x 10(-4)+1.07 x 10(-2)C and A=1.020 x 10(-3)+5.0 x 10(-3)C for methods A and B, respectively. The limits of detection for methods A and B are 1.38 and 0.75 microg ml(-1), respectively. Both methods have been applied successfully for the estimation of rabeprazole sodium in commercial dosage forms. The results are compared with the reference UV spectrophotometric method.     

Determination of Ranitidine Hydrochloride in Pharmaceutical Preparations by Ultraviolet and Visible Spectrophotometry

Abstract

Ranitidine hydrochloride in tablets (T) and injections (I) was determined by ultraviolet spectrophotometry (UVS) at 313 nm and visible spectrophotometry (VISS) at 615 nm, after reaction with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and ferric chloride. For UVS, Beer's law was obeyed in the range 5.0 – 18.0 μg/mL. The coefficients of variation (CV) for the samples T were 0.36% and 0.71% and for the samples I were 0.51% and 0.24%. The recovery average (RA) was 99.88%. For UVS, Beer's law was observed in the range 1.44 – 5.76 μg/mL. The CV for T were 0.72% and 0.59%, and for I were 0.53% and 0.61%. The RA was 99.39%. The precision and accuracy of the two methods were compared.     

A Stability-Indicating LC Method for Assay of Topotecan Hydrochloride

This paper describes the development of a stability-indicating high-performance liquid chromatographic (HPLC) method for quantitative determination of topotecan hydrochloride, a semi-synthetic derivative of camptothecin and anti-tumor drug with topoisomerase I-inhibitory activity. Chromatographic separation was achieved on a C₁₈ column with a mixture of phosphate buffer and acetonitrile as mobile phase. The method was validated for linearity, accuracy, precision, and robustness. Forced degradation studies were performed by treating bulk samples of topotecan hydrochloride with acid (0.5 M hydrochloric acid), base (0.5 M sodium hydroxide), oxidizing agent (10% v/v hydrogen peroxide), heat (60 °C), and UV light (254 nm).     

Highly sensitive and selective spectrophotometric and spectrofluorimetric methods for the determination of ropinirole hydrochloride in tablets

Three sensitive, selective, accurate spectrophotometric and spectrofluorimetric methods have been developed for the determination of ropinirole hydrochloride in tablets. The first method was based on measuring the absorbance of drug solution in methanol at 250 nm. The Beer's law was obeyed in the concentration range 2.5-24 microg ml(-1). The second method was based on the charge transfer reaction of drug, as n-electron donor with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as pi-acceptor in acetonitrile to give radical anions that are measured at 842 nm. The Beer's law was obeyed in the concentration range 0.6-8 microg ml(-1). The third method was based on derivatization reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 followed by measuring the fluorescence intensity at 525 nm with excitation at 464 nm in chloroform. Beer's law was obeyed in the concentration range 0.01-1.3 microg ml(-1). The derivatization reaction product of drug with NBD-Cl was characterized by IR, 1H NMR and mass spectroscopy. The developed methods were validated. The following analytical parameters were investigated: the molar absorptivity (epsilon), limit of detection (LOD, microg ml(-1)) and limit of quantitation (LOQ, microg ml(-1)), precision, accuracy, recovery, and Sandell's sensitivity. Selectivity was validated by subjecting stock solution of ropinirole to acidic, basic, oxidative, and thermal degradation. No interference was observed from common excipients present in formulations. The proposed methods were successfully applied for determination of drug in tablets. The results of these proposed methods were compared with each other statistically.     

Spectrophotometric, spectrofluorimetric, and densitometric methods for the determination of indapamide

Three sensitive spectrophotometric, spectrofluorimetric, and densitometric methods are described for the determination of indapamide. The first and second methods are based on the oxidative coupling reaction of indapamide with 3-methyl-2-benzothiazolinone hydrazone HCl (MBTH) in the presence of cerium(IV) ammonium sulfate in an acidic medium. The absorbance of the reaction product is measured at the lambdamax, 601 nm. With the same reaction, indapamide is determined by its quenching effect on the fluorescence of excess cerous ions at the emission lambdamax, 350 nm, and the excitation at lambdamax, 300 nm. The reaction conditions were optimized, and Beer's law was obeyed for indapamide at 1.2-9.6 microg/mL with mean recoveries of 99.92 +/- 0.83 and 99.97 +/- 1.11%, respectively. The third method, a stability-indicating densitometric assay, was developed for the determination of indapamide, using toluene-ethyl acetate-glacial acetic acid (69 + 30 + 1, v/v/v) as the developing system and scanning at the lambdamax, 242 nm, in the presence of the degradation product and related substance; for the indapamide concentration range of 0.6-6 microg/spot, the mean recovery was 99.73 +/- 0.71%. The proposed methods were successfully applied to the determination of indapamide in bulk powder and commercial tablets, and the results of the analysis agreed statistically with those obtained with the official method. Furthermore, the methods were validated according to the guidelines of the U.S. Pharmacopeia and also assessed by applying the standard additions technique.     

A Sensitive Spectrophotometric Method for the Determination of Some Imidazoline Derivatives by 2,6-Dichlorophenol-Indophenol

Abstract

A new and highly sensitive method is presented for the spectrophotometric determination of four imidazoline derivatives: antazoline hydrochloride, tolazoline hydrochloride, xylometazoline hydrochloride and naphazoline nitrate. The method is based on the reaction of the corresponding drug base with 2,6 - dichlorophenol -indophenol (DGPIP) in chloroform to give a blue chromogen exhibiting a maximum at 588 - 603nm. The method could be applied for the quantitative determination of the above drugs either pure or in their pharmaceutical preparations (tablets and nasal drops). The results obtained are accurate and have good reproducibility.     

Simultaneous determination of ascorbic acid and acetylsalicylic acid in pharmaceutical formulations

A direct, simple, and practical first-derivative spectrophotometric method is described for simultaneous determination of ascorbic acid and acetylsalicylic acid. The effects of the solvent, excipients, and spectral variables on the analytical signal were investigated. The drugs were determined simultaneously with a 0.01 M methanolic hydrochloric acid solution as the solvent, and the signals were evaluated directly by using the zero-crossing method at 245.0 and 256.0 nm for acetylsalicylic acid and ascorbic acid, respectively. The method allows the simultaneous determinations of acetylsalicylic acid and ascorbic acid in the ranges of 6.6 x 10(-6) to 1.5 x 10(-4)M and 3.4 x 10(-6) to 2.0 x 10(-4)M, respectively, with standard deviation of <2.0%. The proposed method was applied to determinations of these drugs in tablets.     

Use of pi-acceptors for spectrophotometric determination of dicyclomine hydrochloride

Simple, rapid, accurate, and sensitive spectrophotometric methods are described for the determination of dicyclomine hydrochloride. The methods are based on the reaction of this drug as an n-electron donor with 2,3-dichloro-5,6-dicyano-p-benzoqunione (DDQ), p-chloranilic acid (p-CA), and chloranil (CL) as pi-acceptors to give highly colored complex species. The colored products are measured spectrophotometrically at 456, 530, and 650 nm for DDQ, p-CA, and CL, respectively. Optimization of the different experimental conditions were studied. Beer's law was obeyed in concentration ranges of 20-100, 50-250, and 80-600 microg/mL for DDQ, pCA, and CL, respectively. Colored complexes are produced in organic solvents and are stable for at least 1 h. The methods were applied to Spasmorest antispasmotic tablets and ampoules with good accuracy and precision.     

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drug with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320 nm or the fluorescence intensity of the produced cerous(III) ion at 363 nm (excitation at 250 nm). Beer's law obeyed from 1.0-7.0 microg ml(-1) and 0.25-2.5 microg ml(-1) acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed methods were successfully applied for determination of the selected drug in its pharmaceutical preparation with good recoveries.     

Spectrophotometric determination of acrivastine in urine and capsules

Three sensitive and accurate spectrophotometric methods are presented for the determination of the antihistaminic acrivastine (ACR) in capsules and urine. The first method utilizes the reaction of 2-nitrophenylhydrazine hydrochloride in presence of dicyclohexylcarbodiimide and pyridine. The violet colour of the resulting acid hydrazide is measured at 550 nm. The second method is based on alkaline oxidation of the drug with potassium permanganate and subsequent measurement of the formed manganate ion at 608 nm. The third method uses derivative spectrophotometry for the determination of ACR. The last method is extended to the in vitro determination of the drug in urine. All methods gave a relative standard deviation of less than 2%.     

Spectrofluorimetric and Spectrophotometric Stability‐Indicating Methods for the Analysis of Veralipride in Presence of Its Degradants and in Spiked Human Plasma

Spectrofluorimetric and spectrophotometric stability‐indicating methods were developed and validated for analysis of veralipride (Ver) in presence of its hydrolytic and oxidative degradants. The spectrofluorimetric method was based on direct measurement of the intrinsic fluorescence of Ver at 366 nm after excitation at 299 nm using sodium lauryl sulfate (SLS) as micelle enhancer. The fluorescence intensity plot was linear over the concentration range 1.0–10.0 µg·mL^?1. The high sensitivity of the method allowed its successful application to the analysis of Ver in spiked human plasma. Two other methods were developed. They are based on the oxidative coupling reaction of Ver with 3‐methyl benzothiazolin‐2‐one hydrazone (MBTH) hydrochloride in presence of ceric ammonium sulphate in an acidic medium. The first method depends on spectrophotometric measurement of the stable green colored oxidative coupling product at 660 nm. The different experimental parameters affecting the reaction were optimized. Linearity range is 10.0–100.0 µg·mL^?1. The second method depends on a fluorescence quenching effect of Ver on the fluorescence of Ce³⁺. The difference in fluorescence intensity was measured at 380 nm after excitation at 300 nm. This method is applicable over the concentration ranges 0.25–2.50 µg·mL^?1. The methods were validated according to the ICH guidelines. They were successfully applied for the analysis of Ver in drug substance, drug product and in laboratory prepared mixtures containing different percentages of hydrolytic and oxidative degradants.     

Thallimetric oxidations-V Titrimetric and spectrophotometric determination of hydrogen peroxide

Titrimetric and spectrophotometric methods have been developed for the determination of hydrogen peroxide at mmole and mumole levels respectively. In these methods thallium(III) is used as the oxidant and the reduced thallium(I) is determined oxidimetrically with potassium bromate in the titrimetric method and by measuring the absorbance of thallium(III) at 260 nm in the presence of 0.1M hydrochloric acid and 1M perchloric acid in the spectrophotometric method. Photochemical redox methods for the estimation of hydrogen peroxide in the presence of a number of diverse ions are described.     

High Performance Liquid Chromatographic Assay of Verapamil Hydrochloride in Dosage Formsk

Abstract

A stability indicating high-performance liquid chromatographic (HPLC) method for determining verapamil hydrochloride in dosage forms is described. The assay affords baseline separation of the drug from its synthesis impurities and from photolytic degradation products, as well as from formulation excipients. The drug was extracted in 0.05 N hydrochloric acid, chromatographed on a C₁₈ reverse-phase column, eluted with methanol-water-acetic acid-triethylamine (55:44:1:0.1) and the effluent was detected at 280 nm. Linearity studies were carried out using peak height or peak area measurements and the detector response to the concentration of verapamil hydrochloride was confirmed. Excellent interlaboratory precision and recovery data were obtained by the spiked placebo method. This procedure was rapid and selective for the assay of the cardiotonic drug. Application of the method for the assay of verapamil hydrochloride in representative dosage forms is described.