Use of Second Derivative Spectrophotometry For the Determination of Certain Cephalosporins and Their Acid-Induced Degradation Products In Combination

Abstract

Methods for determination of individual cephalosporins and their corresponding acid-induced degradation products are described, based upon second derivative spectrophotometry. Linear plots of D₂[dbnd](d²A/dλ²) values with negligible intercept were obtained versus concentration in the range of 0.4–2.4 mg% for both intact and degraded cephalosporins. Kinetic investigation of the cephalosporins degradation proved that the proposed method is applicable to stability determinations Compared with the official method the assay results of the different cephaiosporins pharmaceutical preparations were of equal accuracy (t-test) and reproducibility (F-test).     

Utility of Derivative Spectrophotometry in the Determination of Carbochromen Hydrochloride and Dipyridamole in the Presence of Their Oxidative Degradation Products

Abstract

Direct spectrophotometric methods for the determination of carbochromen hydrochloride and dipyridamole, each in the presence of its oxidative degradation products, are presented. the methods are based on the first derivative (D₁) and second derivative (D₂) spectrophotometric measurement (absolute trough, U) at 336 nm and (Peak-trough, Y) at 309–342 nm for carbochromen hydrochloride and at 240–260 nm(U) and 246–268 nm(Y) for dipyridamole. Plots of D₁ or D₂ versus concentration were linear over the concentration range of 8.00–16.00 μg/ml for carbochromen hydrochloride and 4.00–12.00 μg/ml for dipyridamole. Oxidative degradation of these drugs has been optimized with respect to hydrogen peroxide concentration. Determining the intact in coexistence with its oxidative degradation product, the proposed derivative spectrophotometric methods proved to be of high potential in correcting the systematic error appearing in the results of the A_max method due to the latter. Assaying the commercial tablets, the proposed method gave results of high accuracy and reproducibility.     

Determination of Vitamin A in Presence of its Degradation Product by First - Derivative U.V.- Spectrophotometry

Abstract

A rapid spectrophotometric method for the determination of retinol palmitate (vitamin A) in the presence of its oxidative degradation product is presented. The method is based on the first-derivative measurement of the peak-trough amplitude at 288 – 336 nm. The mean percentage recovery for mixtures of vitamin A with their respective degradation product was 100(1.0). Graphs of log 0% versus time for vitamin A in 0.1 N hydrochloric acid/isopropanol was a straight line with a slope of ?0.0007 min^?1. The method has been succesfuly applied to monitor the vitamin stability.     

Stability-indicating methods for the determination of linezolid in the presence of its alkaline-induced degradation products

Three methods are presented for the determination of linezolid in the presence of its alkaline-induced degradation products. The first method was based on separation of linezolid from its alkaline degradation product by TLC followed by densitometric measurement of the spots of intact drug at 244 nm. The separation was carried out on silica gel 60 F₂₅₄ using isobutanol:ammonia (9:1 v/v) as a mobile phase. The second method was based on first derivative ¹D ultraviolet spectrophotometry with zero crossing point and peak to base measurement. The ¹D value at 251.4 nm was selected for the assay of linezolid in the presence of degradation product. The third method was depended on the first derivative of the ratio spectra ¹DD by measurement of the value at 263.6 nm. The proposed methods were successfully applied to the determination of the drug in bulk powder, in laboratory prepared mixtures with its degradation product and in commercial tablets.     

Third Derivative Spectrophotometric Determination of Metomidate from Aqueous Solution

Abstract

The third derivative spectrophotometric method has been proposed for the determination of metomidate from aqueous solution. By hydrolysis of metomidate, D,L-l-(l-phenylethyl)-imidazole-5-carboxylic acid is formed. Determining the absolute value of the third derivative spectra in the “zero-crossing” point, the concentration of metomidate can be calculated directly without any interferences. The validity of the method was confirmed using synthetic mixtures. Kinetic investigation of the degradation rate of metomidate revealed that the proposed method is stability indicating.     

Synchronized stability indicating RP-LC methods for determination of metolazone with losartan potassium or spironolactone in presence of their degradation products

Abstract

Two precise and selective stability-indicating RP-LC methods have been developed and validated for simultaneous determination of metolazone in its binary mixture with losartan potassium (method 1) and spironolactone (method 2) in the presence of their degradation products. For method 1, the chromatographic separation was achieved on Kromasil C₁₈ column, the mobile phase consisted of a mixture of 0.1% ortho-phosphoric acid in acetonitrile and 0.1% ortho-phosphoric acid in water (28:72, v/v) pumped at flow rate 2?mL/min and UV detection at 235?nm. Linearity was determined over the concentration range of 2–16µg/mL for metolazone and 40–320µg/mL for losartan potassium. For method 2, chromatographic separation of metolazone and spironolactone was achieved on a Symmetry C₈ column using a mobile phase that consisted of acetonitrile, methanol, and 0.1% ortho-phosphoric in water in gradient mode pumped at a flow rate 1.5?mL/min with programed wavelength detection. Linearity was determined over the concentration range of 2–16µg/mL for metolazone and 20–160µg/mL for spironolactone. The suggested methods were proved to be highly selective, precise and accurate for simultaneous determination of the cited drugs in their combined pharmaceutical dosage form in the presence of their degradation products. The proposed methods were validated in compliance with ICH guidelines.

1. Highlights

2. Synchronized determination of metolazone and co-formulated drugs in presence of their degradation products.

3. Act as a method for screening of metolazone and co-formulated drugs in quality control laboratories.

4. Validation of suggested methods according to ICH guidelines.

5. The pathway of degradation of metolazone under different stress conditions was proposed.

     

Stability-Indicating Method for the Determination of Hydrochlorothiazide,Benzydamine Hydrochloride and Clonazepam in the Presence of Their Degradation Products

Abstract

Spectrophotometric, colorimetric and densitometric methods for the determination of hydrochlorothiazide, benzydamine hydrochloride and clonazepam in the presence of their degradation products are described. Hydrochlorothiazide was determined in the presence of its degradation products methoxyhydrothiazide, hydroxyhydrothiazide and 5-chloro-2,4-disulfonamidoaniline applying the first and second derivative spectrophotometer at 278.8 nm and 254.4 nm, respectively, while benzydamine hydrochloride was determined in the presence of its toxic photodegradation products 5-hydroxybenzydamine and 2-B-dimethylaminopropyl-l-benzylindalolin-3-one colorimetrically using the acid dye bromophenol red and measuring the absorbance of the chloroform solution of the ion-pair formed at 425nm. Clonazepam was determined densitometrically in the presence of its degradation products carbostyril and 2-amino-2-chloro-5-nitrobenzophenone. The suggested methods determine hydrochlorothiazide, benzydamine hydrochloride and clonazepam in the presence of degradation products with mean accuracies of 99.57±0.51%, 100.04±0.41%, 100.03±0.21% and 99.84±0.34%, respectively. The proposed methods are suitable for stability testing in bulk powder and in pharmaceutical preparations.     

Selective Differential Spectrophotometric Methods for Determination of Niclosamide and Drotaverine Hydrochloride

ABSTRACT

Differential (ΔA), second derivative (ΔD²) and third derivative (ΔD³) differential ultraviolet spectrophotometric methods have been presented for the quantitation of niclosamide and drotaverine hydrochloride in pure forms and in their pharmaceutical formulations. For niclosamide, the method is based on measuring ΔΔ A, Δ ΔD², A ΔD³ of niclosamide in alkaline solutions against their neutral ethanolic solutions as blanks. For drotaverine hydrochloride, the acidic solutions of the drug are measured against their alkaline solutions as blanks. The proposed methods are sensitive, highly specific and advangageous over the conventional UV assays, since the interference of the excipients, impurities, degradation products or other accompanying drugs is nullified. Accuracy of the analysis with the proposed procedures is significantly greater than the classical spectrophotometric methods.     

Stability-indicating densitometric determination of some antidiabetic drugs in dosage forms, using TLC

The most commonly used antidiabetic sulfonylurea drugs, gliclazide, glipizide and glibenclamide, were determined using stability-indicating densitometric methods. The degradation products were prepared by acid hydrolysis of the intact drugs. Thin layer chromatography was carried out using silica gel 60 F₂₅₄ plates and different mobile phases, followed by scanning of the developed chromatograms. Mixtures of the investigated drugs and their degradation products were prepared and analysed using the proposed methods, with recovery in the range 100.4–101.0% and RSD in the range 0.6–0.7%. Pharmaceutical dosage forms were assayed and found to give results of the same accuracy and reproducibility as official or reference methods.     

Simultaneous Determination of Acetaminophen with Orphenadrine Citrate,Ibuprofen or Chlorzoxazone in Combined Dosage Forms by Zero-Crossing Derivative Spectrophotometry

Abstract

A derivative spectrophotmetric procedure for the simultaneous determination of acetaminophen-orphenadrine citrate, acetaminophen-ibuprofen and acetaminophen-chlorzoxazone, binary mixtures is described. The procedure minimises the mutual interference between these drugs in mixtures and allows the determination of these compounds without a previous extraction step. The precision of the method, expressed as the relative standard deviation, is better than 4%. The method has been successfully applied to laboratory mixtures and commercial tablets containing these drugs.     

Stability-Indicating Chromatographic Methods for Simultaneous Determination of Mosapride and Pantoprazole in Pharmaceutical Dosage Form and Plasma Samples

Simple, sensitive, selective, precise, and stability-indicating thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) methods for the determination of mosapride and pantoprazole in pharmaceutical tablets were developed and validated as per the International Conference on Harmonization guidelines. The TLC method employs aluminum TLC plates precoated with silica gel 60F₂₅₄ as the stationary phase and ethyl acetate/methanol/toluene (4:1:2, v/v/v) as the mobile phase to give compact spots for mosapride (R _f 0.73) and pantoprazole (R _f 0.45) separated from their degradation products; the chromatogram was scanned at 276 nm. The HPLC method utilizes a C18 column and a mobile phase consisting of acetonitrile/methanol/20 mM ammonium acetate (4:2:4, v/v/v) at a flow rate of 1.0 mL min⁻¹ for the separation of mosapride (t _R 11.4) and pantoprazole (t _R 4.4) from their degradation products. Quantitation was achieved with UV detection at 280 nm. The same HPLC method was successfully used in performing calibrations in lower concentration ranges for both drugs in human plasma using ezetimibe as internal standard. The methods were validated in terms of accuracy, precision, linearity, limits of detection, and limits of quantification. Mosapride and pantoprazole were exposed to acid hydrolysis and then analyzed by the proposed methods. As the methods could effectively separate the drugs from their degradation products, these techniques can be employed as stability-indicating methods that have been successively applied to pharmaceutical formulations without interference from the excipients. Moreover the HPLC method was successfully used in the determination of both drugs in spiked human plasma.

     

Stability-Indicating Chromatographic Methods for Simultaneous Determination of Mosapride and Pantoprazole in Pharmaceutical Dosage Form and Plasma Samples

Simple, sensitive, selective, precise, and stability-indicating thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) methods for the determination of mosapride and pantoprazole in pharmaceutical tablets were developed and validated as per the International Conference on Harmonization guidelines. The TLC method employs aluminum TLC plates precoated with silica gel 60F₂₅₄ as the stationary phase and ethyl acetate/methanol/toluene (4:1:2, v/v/v) as the mobile phase to give compact spots for mosapride (R _f 0.73) and pantoprazole (R _f 0.45) separated from their degradation products; the chromatogram was scanned at 276 nm. The HPLC method utilizes a C18 column and a mobile phase consisting of acetonitrile/methanol/20 mM ammonium acetate (4:2:4, v/v/v) at a flow rate of 1.0 mL min^?1 for the separation of mosapride (t _R 11.4) and pantoprazole (t _R 4.4) from their degradation products. Quantitation was achieved with UV detection at 280 nm. The same HPLC method was successfully used in performing calibrations in lower concentration ranges for both drugs in human plasma using ezetimibe as internal standard. The methods were validated in terms of accuracy, precision, linearity, limits of detection, and limits of quantification. Mosapride and pantoprazole were exposed to acid hydrolysis and then analyzed by the proposed methods. As the methods could effectively separate the drugs from their degradation products, these techniques can be employed as stability-indicating methods that have been successively applied to pharmaceutical formulations without interference from the excipients. Moreover the HPLC method was successfully used in the determination of both drugs in spiked human plasma.     

Simultaneous Quantitation of Minoxidil and Tretinoin in Magistral and Pharmaceutical Preparations by First Derivative Spectrophotometry

Abstract

A first derivative spectrophotometry method has been developed for the simultaneous quantitation of minoxidil and tretinoin. The method is based on measuring the first derivative signals (D₁) of minoxidil and tretinoin at 290 and 351 nm, respectively, without any interference from each other, or any other coexisting materials. Beer's law was valid over the concentration range 2–10 μg/ml of minoxidil and 0.25–1.25 μg/ml of tretinoin. The proposed method has been applied successfully to the determination of some magistral and pharmaceutical preparations. Relative standard deviations for the assay of both drugs were less than 0.95%.     

Stability-Indicating Method For The Determination Of N-Desmethyldiazepam And Simultaneous Determination Of Its Degradation Products

Abstract

A simple, direct and sensitive spectrophotometric method for the determination of the intact N-desmethyldiazepam in the presence of its degradation products, 2-amino-5-chlorobenzophenone and glycine, is developed. The proposed procedure is based on direct measurement of the absorbance of its acidified methanolic solution at 361 nm. The procedure determines 8–56 mcg ml^?1 of N-desmethyldiazepam with an accuracy of 100.2 ± 0.51%. The proposed procedure retains its accuracy in presence of up to 80% of the different degradation products. The procedure is applied successfully for the determination of N-desmethyldiazepam in bulk powder, tablets and drops.

Simultaneous determination of the different degradation products in the presence of the parent drug is also described. Thus, 2-amino-5-chlorobenzophenone is determined by direct measurement of its methanolic solution at about 380 nm, with an accuracy of 100.4 ± 0.42%. Glycine is determined colorimetrically using ninhydrin reagent in presence of pyridine, with an accuracy of 99.5 ± 0.78%.     

Application of Derivative and Ratio Spectra Derivative Spectrophotometry for the Determination of Pseudoephedrine Hydrochloride and Acrivastine in Capsules

Abstract

Two new spectrophotometric methods are used for the determination of acrivastine and pseudoephedrine hydochloride in their mixture without previous chemical separation. In the first, second derivative spectrophotometry, the measurements are made at 288.0 nm for acrivastine and at 270.2 nm for pseudoephedrine hydrochloride in the second derivative spectra of their solution in 0.1M NaOH. In the second, ratio spectra derivative spectrophotometry, the amplitudes are measured at 276.0 nm and 298.5 nm corresponding to two maximums for acrivastine, and at 252.6 nm and 268.3 nm corresponding to a maximum and a minumum, respectively, for pseudoephedrine hydrochloride in first derivative of their ratio spectra plotted by using of their solutions as divisor. The methods were successfully applied for the determination of these drugs in a commercial pharmaceutical formulation capsule.     

Atomic Emission Spectrometric Determination of Antazoline,Hydralazine, Amiloride,Thiamine and Quinine Based on Formation of Ion Associates with Ammonium Reineckate.

Abstract

Ion-associate complexes of Antazoline HC1 (I), Hydralazine HC1 (II), Amiloride HC1 (III), Thiamine HC1 (IV) and Quinine sulphate (V) with ammonium reineckate were precipitated and their solubilities were studied as a function of pH, ionic strength and temperature. Saturated solutions of each ion-associate under the optimum precipitation conditions were prepared and the metal ion-content in the supernatent was determined. The solubility products were thus elucidated at different temperatures. A new accurate and precise method using direct coupled plasma-atomic emission spectrometry for the determination of the investigated drugs in pure solutions and in pharmaceutical preparations is described. The drugs can be determined by the present method in the ranges 0.3-3.0, 0.19-1.96, 0.3-3.0, 0.33-3.37 and 0.78-7.82 mg/25 ml solutions of I, II, III, IV and V, respectively.     

Characterization of degradation products of poly[(3,3,3-trifluoropropyl)methylsiloxane] by nuclear magnetic resonance spectroscopy, mass spectrometry and gas chromatography

Poly[(3,3,3-trifluoropropyl)methylsiloxane] (PTFPMS) was treated with the solvents acetone, ethyl acetate and methanol and its degradation products were analyzed with multiple techniques. ¹H, ²⁹Si and ¹⁹F nuclear magnetic resonance (NMR) spectroscopy were useful for the characterization of the intact polymers and for the determination of cyclosiloxanes. Cyclosiloxanes with a ring size of up to 23 were quantified by gas chromatography. The only degradation products found were TFPmethyl-cyclosiloxanes. 1,3,5,7-Tetrakis(TFPmethyl)-cyclotetrasiloxane was predominant, and (TFPmethyl)cyclotri-, penta- and hexasiloxane could be detected at lower concentrations. The identity of cyclic degradation products with a ring size of up to 6 was unambiguously confirmed by direct infusion mass spectrometry. The TFPmethyl-cyclosiloxanes were successfully ionized by electrospray ionization in the negative mode. None of the techniques applied gave hints to other degradation products such as short linear oligomers. Almost complete degradation of PTFPMS occurred in acetone and methanol, while degradation is distinctly reduced in ethyl acetate.     

Field Desorption Mass Spectrometry

Field desorption (FD) enables mass-spectrometric investigation of large organic molecules without their vaporization. The present state of our theoretical understanding of the ionization of these molecules in the adsorbed state on organic emitters is described. The special problems of the technique and prospective developments in the apparatus for future analytical problems are outlined. The present progress report concentrates on analytical studies of biochemical model compounds and degradation products from environmental chemicals and drugs. The method is particularly suitable for the detection and identification of submicrogram quantities of underivatized polar substances present in complex mixtures or pre-purified extracts from biological materials.     

贫电子环丙烷衍生物与2-巯基苯骈噻唑的反应研究

贫电子环丙烷衍生物1以精制四氢呋喃为溶剂, 与2-巯基苯骈噻唑(2)封管加热反应, 得到产物3和4. 产物3经IR, MS, ¹H NMR, ¹³C NMR和元素分析等数据确定其结构为: (R)-β-取代-(R)-γ-(2-巯基)苯骈噻唑基-γ-对位取代苯基丁酸或(S)-β-取代-(S)-γ-(2-巯基)苯骈噻唑基-γ-对位取代苯基丁酸(3); 产物4通过IR, MS, ¹H NMR, ¹³C NMR, 2D-NOESY谱和元素分析等数据确定其结构为: 反式-β-取代-γ-对位取代苯基-3-丁烯酸(4). 对生成产物的机理也进行了推测.     

Simultaneous Determination of Cilazapril and Hydrochlorothiazide in Tablets by Spectrophotometric Methods

Abstract

In this study, two new spectrophotometric methods were used for the simultaneous determination of cilazapril and hydrochlorothiazide in their binary mixture. In the first method, derivative spectrophotometry, dA/dδ values were measured at 242.8 nm and 282.8 nm for cilazapril and hydrochlorothiazide, respectively, in the first derivative spectra of their combination. The relative standard deviation of the method was found to be 0.77% for cilazapril and 0.24% for hydrochlorothiazide. In the second, the absorbancy ratio method, the quantification of cilazapril and hydrochlorothiazide was performed by using the absorbances read at 210.4 nm. 250.2 nm and 270.6 nm in the zero-order spectra of their mixture; relative standard deviations of the method were found to be 1.26 % and 0.81 % for cilazapril and hydrochlorothiazide, respectively. These two methods have been successfully applied to a tablet containing these drugs.