Spectrophotometric Assay of Certain Cardiovascular Drugs Through Charge Transfer Reactions

Abstract

Charge transfer reaction is described for the assay of certain cardiovascular drugs; carbochromen hydrochloride, verapamil hydrochloride, acebutolol hydrochloride, carazolol and propranolol hydrochloride. the three acceptors, p-chloranilic acid (p-CA), dichlorophenyl-indophenol (DCPIP) and 2,3-dichloro 5,6-dicyano p-benzoquinone (DDQ) have been used to carry out such assay. the reaction is based on the proton transfer from the p-CA to the drug base or electron transfer from the drug base to either DCPIP or DDQ and the subsequent possible formation of resonance hybrids of charge transfer complexes. Optimization of the reaction conditions has been investigated. Obediance to Beer's law permitted the assay of these drugs in their dosage form. Calculating log ε for different chromogens, the method sensitivity is decreasing in order of using DCPIP, DDQ & p-CA. the method has been compared with the traditional U.V. absorbance spectrophotometric method and found to be of equal accuracy (t-test) and equal reproducibility)(F-test).     

Determination of Naloxone Hydrochloride in Dosage form by High-Performance Liquid Chromatography

Abstract

A new, sensitive and rapid method for the determination of naloxone hydrochloride as drug in dosage entity and form using HPLC has been developed. Authentic naloxone hydrochloride was used to establish a calibration curve. A linear relationship was obtained for concentrations ranging from 10 μg/ml to 50 μg/ml. The column used was C₁₈, Micropak MCH-10 (monomeric) and the mobile phase was acetonitrile : 0.01 M KH₂PO₄ (70 : 30) at a flow rate of 2 ml/min. Retention time for naloxone hydrochloride was 3.3 minutes. The proposed method has been proved accurate and precise compared to other pharmacopoeia methods of assay for naloxone hydrochloride.     

High Performance Liquid Chromatographic Assay of Hydromorphone Hydrochloride Injection

Abstract

A stability indicating high performance liquid chromatographic (HPLC) method for determining hydromorphone hydrochloride in dosage forms is described. The drug was chromatographed on a C₁₈ reverse phase column, using a mobile phase consisting of sodium lauryl sulfate, acetic acid, acetonitrile and water, and detected at 280 nm. Linearity of detector response to the concentration was confirmed. The procedure showed excellent reproducibility and gave quantitative recoveries of the drug from spiked placebos. Photodegraded samples of the dosage form, were assayed by the HPLC procedure and the current USP spectrophotometric procedure. Comparison of the results showed that the USP procedure is only partially stability indicating.     

Simultaneous Determination of Hydrochlorothiazide and Propranolol Hydrochloride in Tablets by High-Performance Liquid Chromatography

Abstract

A simple and stability indicating HPLC procedure is described for the simultaneous determination of hydrochlorothiazide and propranolol hydrochloride in tablet formulations. Potential degradation products of both drugs and synthesis impurities of hydrochlorothiazide were separated, making the determination stability indicating for both drugs and selective for hydrochlorothiazide. All compounds were chromatographed on a cyanopropylsilane column, eluted with a 15:85 mixture of acetonitrile: 0.05 M ammonium phosphate (pH 3.0) and detected at 290 m. Excellent interlaboratory precision and recovery data were obtained. Linearity studies were carried out using peak area measurements. Detector response to the concentration of each drug was confirmed. The method was applied to dosage forms containing 25 mg of hydrochlorothiazide and 40 or 80 mg of propranolol hydrochloride.     

Quantitation of Hydralazine Hydro-Chloride in Pharmaceutical Dosage Forms Using Highc Performance Liquid Chromatography

Abstract

Stability-indicating assay methods for the quantitation of hydralazine hydrochloride based on high-performance liquid chroma-tography using two different columns have been developed. Phenyl-prooanolamine can be used as an internal standard with both columns (μC₁₈ and μphenyl) while hydrochlorothiazide can be used only with μphenyl column. The method is accurate and precise with percent relative standard deviations based on 6 readings of less than 2. The excipients present in the dosage forms did not interfere with the assay method. In combination with hydrochlorothiazide, hydralazine can be quantified only with μphenyl column. Two oral liquid dosage forms prepared in a local hospital using commercially available strawberry syrup/simple syrup decomposed completely in one day.     

Determination of Some Pharmaceutically – Important Aminoquinoline Antimalarials,via Charge – Transfer Complexes

Abstract

A simple and rapid spectrophotometric method for the assay of amodiaquine hydrochloride, chloroquine phosphate and primaquine phosphate is described. The method is based on the interaction of the drug with 7, 7, 8, 8-tetracyanoquinodimethane (TCNQ) as a π-electron acceptor, forming a highly coloured stable radical anion. The molecular ratios of the reactants in the complexes as well as the experimental conditions leading to maximum charge-transfer bands have been studied. Beer's Law is obeyed over aminoquinoline antimalarials concentration range of 0.4–4.0 ug.ml^?1. The proposed procedure has been applied successfully to the analysis of antimalarials in their dosage forms and the results are in agreement with those of official methods.     

Rapid Quantitation of Verapamil in Plasma by High-Performance Liquid Chromatography

Abstract

A simple and sensitive liquid chromatographic assay procedure using a fluorescence detector for the quantitative determination of verapamil in plasma without extraction was developed. After precipitating the protein with acetonitrile, the resulting supernatant liquid was injected onto the column for analysis. Chromatographic separation was achieved on C₁₈ reversed phase column and the eluting solvent was the isocratic mixture of methanol, acetonitrile and pH 3.0 glycine buffer (1:4:5). With this mobile phase the drug and its internal standard were well separated from the interference of the plasma sample. The average recovery of verapamil from 3 replicate samples of different concentration (100–600 ng/mL) were 95.5 ± 5.68%. The minimum amount of verapamil detectable by this method was 40 ng/mL of sample. The elimination half-life (β-phase) of this drug in rabbits was found to be 3.7 hours.     

Determination of Bretylium in Pharmaceutical Dosage Forms

Abstract

A simple, high-pressure liquid chromatographic method for determination of bretylium in pharmaceutical dosage forms is described. The sensitivity of the method is 50 ng with high reproducibility. Exogenous additives from injection, infusion or tablet dosage forms do not interfere with the assay. An increase in the pH of the sample, however, caused a decrease in the peak height of bretylium. Bretylium is a chemically stable compound. Under conditions of either 1.5 N hydrochloric acid, nitric acid, or sodium hydroxide at 25°C and 100°C for a period of up to 48 hours did not influence the outcome of the assay.     

LC Assay for Ciprofloxacin Hydrochloride Ophthalmic Solution

The objective of the current study was to develop and subsequently validate a simple, sensitive and precise reversed-phase LC method for the determination of ciprofloxacin hydrochloride in ophthalmic solution form. The chromatographic separation of ciprofloxacin hydrochloride was achieved on a Symmetry Waters C₁₈ column using UV detection at 275 nm. The optimized mobile phase consisted of 2.5% acetic acid solution: methanol:acetonitrile (70:15:15, v/v/v). The proposed method provided linear responses within the concentration range 1.0–6.0 μg mL⁻¹ for ciprofloxacin hydrochloride. Correlation coefficient (r) for the ciprofloxacin hydrochloride was 0.9994. The precision of the method was demonstrated using intra- and inter-day assay RSD% values which were less than 5% in all instances. No interference from any components of pharmaceutical dosage forms was observed.

     

LC Assay for Ciprofloxacin Hydrochloride Ophthalmic Solution

The objective of the current study was to develop and subsequently validate a simple, sensitive and precise reversed-phase LC method for the determination of ciprofloxacin hydrochloride in ophthalmic solution form. The chromatographic separation of ciprofloxacin hydrochloride was achieved on a Symmetry Waters C₁₈ column using UV detection at 275 nm. The optimized mobile phase consisted of 2.5% acetic acid solution: methanol:acetonitrile (70:15:15, v/v/v). The proposed method provided linear responses within the concentration range 1.0–6.0 μg mL⁻¹ for ciprofloxacin hydrochloride. Correlation coefficient (r) for the ciprofloxacin hydrochloride was 0.9994. The precision of the method was demonstrated using intra- and inter-day assay RSD% values which were less than 5% in all instances. No interference from any components of pharmaceutical dosage forms was observed.     

Simultaneous Quantitative Determination of Codeine Phosphate,Chlorpheniramine Maleate Phenylephrine Hydrochloride and Acetaminophen in Pharmaceutical Dosage Forms Using Thin Layer Chromatography Densitometry

Abstract

A simple and specific method for the analysis of codeine phosphate, chlorpheniramine maleate, phenylephrine hydrochloride and acetaminophen in pharmaceutical dosage forms was developed. The procedure consists of direct application of diluted liquid dosage forms and the solutions of solid dosage forms on silica gel plates. The mobile phase for development consisted of n-butanol-methanol-toluene-water and acetic acid. The separated components were measured quantitatively by densitometry. Linearity, reproducibility and percentage recovery of active ingredients from dosage forms were calculated.     

Charge-Transfer Complexation for Spectrophotometric Assay of Certain Imidazole Antifungal Drugs

Abstract

A spectrophotometric method is described for the assay of some antifungal agents containing an imidazole ring: clotrimazole, econazole, ketoconazole and miconazole. The method is based on the formation of a charge-transfer complex between the drug as n-electron donor and iodine as [sgrave]-acceptor. The product exhibited two absorption maxima at 290 and 377 nm; measurements are made at 290 nm. Beer's law is obeyed in a concentration range of 1-40 μg/ml. The method is rapid, simple and sensitive and can be applied to the analysis of some commercial dosage forms without interference. A detailed investigation of the formed complex was made with respect to its composition, association constant and free energy change.

     

A HPLC Method for the Determination of Butaperazine in Solutions,Tablets, Plasma and Bile

Abstract

A specific HPLC method for the determination of the antipsychotic drug butaperazine (B) in solutions, tablets, plasma and bile has been developed. The instrument used was a Waters HPLC equipped with a Model 440 Spectrometer and a μ-Bondapak-NH₂ column. The mobile phase, chloroform-methanol (100:3.5) was pumped at a rate of 1.5 ml per minute. Ultraviolet absorbance at a wave length of 280 nm was used for detection. The procedure involved the extraction of the drug from the dosage forms with chloroform and from plasma and bile with hexaneisopropanol (9:1). Hydrocortisone acetate was used as the internal standard. Retention times of 2.4 and 3.9 minutes were obtained for the internal standard and B respectively. Analytical calibration yielded a linear relationship from 0.1–25 μg per ml, with r² value of 0.99. The percentage recovery of B averaged 99% from the dosage forms and 94% from the biological fluids. An improvement in the method for determining B in bile and plasma was later developed. It involved the use of a different mobile phase and detecting the drug fluorometrically.     

A Validated Stability-Indicating TLC Method for Determination of Forskolin in Crude Drug and Pharmaceutical Dosage Form

A simple, accurate, selective, precise, economical and stability-indicating high-performance thin-layer chromatographic method for analysis of forskolin in crude drug and in pharmaceutical dosage form was developed and validated. The method was developed on TLC aluminium plates precoated with silica gel 60F-254 using solvent system benzene:methanol (9:1, v/v), which gives compact spot of forskolin (R _f value 0.25 ± 0.02). Densitometric analysis of forskolin was carried out in the absorbance mode at 545 nm after spraying with anisaldehyde sulphuric acid. The linear regression analysis data for the calibration plots showed good linear relationship with r = 0.994 and 0.994 with respect to peak height and peak area, respectively, in the concentration range 100–1,000 ng per spot. The limits of detection and quantification were 8.1 and 26.9 ng per spot, respectively. The proposed method was applied for determination of forskolin in Coleus forskohlii root and in capsule dosage forms, which showed 0.18 and 0.57% w/w of forskolin. Forskolin was subjected to acid and alkali hydrolysis, oxidation, photodegradation and heat degradation. It was observed that the drug is susceptible to acid, base hydrolysis, oxidation, photo-oxidation and heat degradation. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of forskolin in crude drug and in pharmaceutical dosage forms. The developed method effectively resolved the forskolin from components of C. forskohlii root, from excipients of capsule as well as the degradation products of forskolin hence, it can be employed for routine analysis and as a stability-indicating method.     

First-Derivative Spectrophotometric Determination of a Mixture of Pirbuterol Hydrochloride and Butorphanol Tartrate

Abstract

Vierordt's method, its modified version and the first derivative method have been applied for the simultaneous determination of butorphanol tartrate and pirbuterol hydrochloride in laboratory mixtures of authemtic and dosage forms. The first derivative spectrophotometric method yields accurate and reprodeucible results for both drugs. Mean percent recoveries for butorphanol tartrate and pirbuterol hydrochloride in dosage forms were 100.54±0.84 and 100.42±1.27, respectively. Virrordt's method and its modified version have given unreliable results; the reasons behind have been discussed.     

Spectrophotometric Determination of Etilefrine,Ritodrine, Isoxsuprine and Salbutamol by Nitration and Subsequent Meisenheimer Complex Formation

Abstract

A simple and sensitive colorimetric method has been developed for the determination of four phenolic drugs, namely, etilefrine hydrochloride, ritodrine hydrochloride, isoxsuprine hydrochloride and salbutamol sulphate. The method is, mainly, based on the nitration of the drug molecule followed by the subsequent formation of meisenheimer complex with a nucleophilic reagent (acetone) in alkaline medium. The experimental conditions leading to optimum chromogen intensity and stability were carefully studied and incorporated in the general procedure. Under the proposed conditions, the method was applicable over the concentration range of 4.8–16 μg ml^?1 for the four drugs. The suggested method was further applied for the determination of the studied drugs in bulk and pharmaceutical dosage forms. The results of the analysis were found to agree statistically with those obtained with either the official or the referee methods. The procedure is characterized by its simplicity with accuracy and precision.     

Electrochemical Oxidation of Phenothiazine Derivatives at Glassy Carbon Electrodes and Their Differential Pulse and Square‐wave Voltammetric Determination in Pharmaceuticals

Abstract

Three 2,10‐disubstituted phenothiazines—chlorpromazine hydrochloride (CPM), thioridazine hydrochloride (TR) and propericiazine (PRC)—were electrochemically studied in various buffer systems at different pH values, using a glassy carbon electrode. The substances were electrochemically oxidized at potential range 0.55–0.75 V. The oxidation was reversible and exhibited diffusion‐controlled process. The mechanism of the oxidation process is discussed. According to the linear relation between peak current and concentration, differential pulse voltammetry (DPV) and square wave voltammetry (SWV) methods for quantitative determination of chlorpromazine and propericiazine in 0.1 M HClO₄, and thioridazine in pH 2 phosphate buffer, was applied. Both the repeatability and reproducibility of the methods were also determined for all studied substances. The developed procedures were successfully applied to the determination of chlorpromazine and thioridazine in pharmaceutical dosage forms.     

Spectrophotometric Determination of Chlorpheniramine in Some Dosage Forms Using the Charge – Transfer Complexation Technique

SUMMARY

A spectrophotometric method of assay of chlorpheniramine in some of its dosage forms based on the principle of charge transfer complexation between chlorpheniramine (the n – donor) and chloranilic acid (the π - acceptor) is described.

A 1:1 molecular complex with maximum absorption at 530 nm was formed. The association constant, molar absorptivity, and free energy change of the complex indicate that the complex has high stability. Beer's law was obeyed within the concentration range of 2 to 24 mg% (0.2 to 0.24 mg/ml.). The sensitivity of this method is 4.02 x 10^?5M of chlorpheniramine base. There were high percentage recoveries when the method was employed to the quantitative determination of chlorpheniramine from commercial tablets and injection. This newly proposed method is easy, fast and requires minimum chemicals and equipment, and, therefore, could be utilized in the assay of chlorpheniramine in dosage forms.     

Spectrophotometric Determination of Some Cardiovascular Drugs Using P-Chloranilic Acid

Abstract

A simple and sensitive spectrophotometric method for the assay of some cardio-vascular drugs is described. The method is based on the interaction of the drug and p-chloranilic acid (p-CA) to give a stable and intensively coloured ion-pair salt. The drugs used are quinidine sulphate, prenylamine lactate, dipyridamol, hydralazine hydrochloride, tolazoline hydrochloride and pindolol. The optimum experimental conditions for colour development have been studied. Conformity to Beer's law enabled the determination of these drugs in their pharmaceutical preparations. The assay results are in accord with the pharmacopoeal assay results.     

Reversed-Phase High Performance Liquid Chromatographic and Thin Layer Chromatographic Methods for the Simultaneous Determination of Benazepril Hydrochloride and Hydrochlorothiazide in Cibadrex Tablets

ABSTRACT

Two procedures were developed for simultaneous determination of benazepril hydrochloride (I) and hydrochlorothiazide (II) in pure, laboratory made mixtures and in pharmaceutical dosage form “Cibadrex tablets® using reversed phase high performance liquid chromatographic and thin layer chromatographic methods.

For reversed phase HPLC, a new very sensitive, rapid, selective method was developed. The linearity ranges were 32-448 ng/20 μl and 40-560 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide, respectively. The corresponding recoveries were 99.38 ± 1.526 and 99.2 ± 1.123.

The minimum detection limits were 7 ng/20 μl and 14 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide respectively.

On the other hand, a new, simple, sensitive and fast thin layer chromatographic scanning densitometric method was developed for simultaneous determination of benazepril hydrochloride and hydrochlorothiazide using ethyl acetate: methanol: ammonia (85: 20: 10 v/v) as the developing system. The R_f values were 0.33 & 0.68 for benazepril hydrochloride and hydrochlorothiazide respectively. The minimum detection limit obtained was 0.12 μg/spot for benazepril hydrochloride and 0.24 μg/spot for hydrochlorothiazide. The mean percentage recoveries were 100.04 ± 1.102 and 99.31 ± 1.009 for benazepril hydrochloride and hydrochlorothiazide respectively.

The two proposed methods were simple, precise, sensitive and could be successfully applied for the determination of pure, laboratory made mixtures and pharmaceutical dosage forms. The results obtained were compared with those obtained by A ^1%.