Validated Stability-Indicating Chromatographic Method for the Assay of Erlotinib Active Pharmaceutical Ingredient

Abstract

A simple stability-indicating high-performance liquid-chromatographic (HPLC) method for the assay of erlotinib in the presence of its degradation products was developed on a C18 column using a mobile phase of 0.01 M ammonium formate–acetonitrile–containing formic acid with a flow rate of 1.0 mL min^?1. The method was validated. Selectivity was validated by subjecting the stock solution of erlotinib to acidic, basic, photolysis, oxidative, and thermal degradation. The linearity range and values for limits of detection (LOD) and quantification (LOQ) were found to be 1–198, 0.33, and 1.1 µg mL^?1, respectively. The analysis of the tablets containing erlotinib was quite precise (relative standard deviation <1%).     

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.     

Application of Continuous Kinetics to Polymer Degradation

Abstract

Degradation of polydisperse polymers is studied in the framework of continuous kinetics which is directly based on continuous distribution functions which depend on the molecular weight and the time. A firstorder formalism is presumed. A Schulz-Flory distribution (with time-dependent parameters) is assumed to be valid during the entire time of degradation. Thus, an essential simplification of the solution procedure of the continuous rate equation is achieved. As a proof of accuracy, the approximation solution and the exact solution are compared for the case of “random scission.” Furthermore, the developed method is shown to be suitable for describing the experimental data of dextran degradation caused by acid hydrolysis, by ultrasonic irradiation, and by enzymatic attack. The model parameters fitted to the experimental data allow the evaluation of the scission probability as a function of the molecular weight and of the location of the bond to be broken within the molecule.     

HPLC-UV Assay Method for Clindamycin Palmitate Hydrochloride as Drug Substance and Oral Solution

Abstract

A simple isocratic high performance liquid chromatography (HPLC) method was developed for the determination of Clindamycin palmitate hydrochloride in drug substance and oral solutions. The XTerra RP18 250 mm × 4.6 mm × 5 µ column was used as stationary phase, and the mobile phase was a 0.5% solution of Triethylamine in a 1:9 (v/v) water:methanol mixture adjusted to pH 5.0 with orthophosphoric acid. The detector wavelength was selected at 210 nm and flow rate was maintained at 1.50 ml/min. Forced degradation studies were performed for drug substance, 75 mg/5 ml oral solution and placebo, using acid, base, oxidation, temperature, humidity, and photolytic degradation to demonstrate the specificity of the method. The developed method was validated as per ICH method validation guidelines.     

Stability Indicating Hplc Method for the Determination of Sparfloxacin (Spar)

ABSTRACT

A rapid, sensitive and stability indicating method for the determination of sparfloxacin (SPAR) by RP - HPLC has been developed on a Merck RP - Select B (5 μm; 12.5 cm x 4.0 mm) column using a mobile phase of water: acetonitrile: triethylamine (80 : 20 : 0.2 v/v) pH of which was adjusted to 2.6 with orthrophosphoric acid. The flow rate was 1 ml / min. and the detection was carried out at 304 nm using Waters 486 variable wavelength detector. The retention time for SPAR was 7.2 min. Linearity range was from 8 - 1000 ppm. The method showed good precision and accuracy when applied to two brands of tablets containing SPAR. In alkaline media SPAR is stable where as it undergoes degradation in acidic and oxidising conditions generating different degradation products the nature of which is required to be established. The proposed method nicely separates the degraded products from SPAR and hence can be used as stability indicating method for the assay of SPAR.     

A Stability-Indicating Hplc Analysis of Famotidine and Its Application to Kinetic Studies

Abstract

A stability-indicating HPLC analytical method has been developed for the determination of the H₂-receptor antagonist, famotidine in the presence of its degradation products. the method utilizes reversed phase chromatography with UV detection and internal calibration techniques. the mobile phase was comprised of 84% ammonium acetate buffer (pH 2.9) and 16% acetonitrile and pumped at a flow rate of 1.5 ml/min. Quantitation was performed by measuring the peak height ratio of drug to internal standard (salicylic acid). the limit of famotidine detection was determined to be 10 ng (0.4 ug/ml) with a signal to noise ratio of 3:1. Within day coefficient of variation of the method was 2.22% (2.5 μg/ml) and 0.82% (10 μg/ml). Between day coefficient of variation based on the slopes of daily prepared standard curves was 4.70%. the developed method was used to determine the drug content of famotidine tablets. Further, it was used to investigate the kinetics of degradation of the drug in an acidic solution.     

GLC and HPLC Determination of Diazepam and its Degradation Products in Pharmaceutical formulations

Abstract

Stability-indicating high performance liquid chromatographic (HPLC) and gas-liquid chromatographic (GLC) assays for diazepam in pharmaceutical formulations are described. In HPLC method, the material is extracted with 5 % aqueous methanol and chromatographed on a dimethyloctyl stationary phase using methanol-water-acetic acid (80: 20: 1) and propyl paraben internal standard. The system separated diazepam from the main degradation products, desmethyl diazepam (a synthetic precursor of diazepam) and the excipients present in ampoules and syrups. The GLC method included the extraction of diazepam and 2-methylamino-5-chiorobenzo-phenone (MACB) from aqueous acidic solution into chloro form leaving the other degradation products in the aqueous phase. The chloroform extract is evaporated to dryness, dissolved in chloroform containing diethylhexyl phtha-late as internal standard and chromatographed on an OV-17 stationary phase using flame ionisation detector. The results are compared with the BP method described for each formulation.     

Stability-Specific HPLC Analysis of the Antiulcer Prostaglandin,Enprostil, in a Soft Elastic Gelatin Capsule Formulation

Abstract

This report describes a reverse-phase HPLC assay for the antiulcer drug, enprostil, formulated as a 0.3 mM solution (in propylene carbonate) filled into soft elastic gelatin capsules. The method uses: a 5 μm C18 column, a ternary (THF-methanol-phosphate buffer) mobile phase and 220 nm spectrophotometric detection to provide a sensitive and specific assay for enprostil and its major degradation products. The method satisfies the usual statistical criteria (recovery efficiency, response linearity, precision, lower quantitation limit) and performs well under various operating conditions as demonstrated by system suitability tests (analyte capacity factor dependence on column type, mobile phase composition, flow rate, and column temperature). We also demonstrate how a diode-array spectrophotometric detector     

Kinetics of degradation of Lycium barbarum polysaccharide by ultrasonication

Lycium barbarum polysaccharide (LBP) was subjected to ultrasonic degradation under the controlled conditions, such as, temperature, irradiation time, initial pH value, and concentration of solution. The ultrasonic degradation of LBP was demonstrated by the changes of intrinsic viscosity. Viscometry was used to study the degradation behavior and a kinetic model was developed to estimate the degradation rate. The results showed that the degradation rate was reduced with the increase of solution concentration and pH, and increased with increase of temperature. The relationship between the number average molar mass (M_n) and intrinsic viscosities as interpreted using the Mark‐Houwink equation suggested that LBP adopted a flexible coil conformation in aqueous solution. The activation energy of ultrasonic degradation of LBP is 26.5 kJ/mol, which indicates that the ultrasonic degradation is a convenient, time saving, and cost‐efficient method for obtaining a desired molecular weight. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 509–513, 2010     

The Preparation and Biodegradable Properties of Poly(L‐lactic acid)‐Poly(ϵ‐caprolactone) Multiblock Copolymers

Multi‐block copolymers of PLLA and PCL were prepared by a coupling reaction between PLLA and PCL prepolymers with –NCO end groups. FTIR proved that the products were PLLA‐PCL copolymers. The weight‐average molecular weight of the copolymers was up to 180,000 at a composition of 60% PLLA and 40% PCL. The degradation properties of PLLA and PLLA‐PCL copolymers were studied by a soil burial test and a hydrolysis test in a phosphate‐buffer solution. The degradation rate was estimated by the mass loss, molecular weight reduction, pH value changes and swelling index; the degradation rates of the copolymers were a function of the composition of PLLA and PCL. Increasing PCL content in the copolymers resulted in lower degradation rate.     

Two multifunctional organic-inorganic hybrid complexes based on polyoxometalates,BiEDTA and sodium linker: crystal structures,photochromic, and catalytic performances

Two 3-D organic–inorganic hybrid supermolecular complexes, Na(BiHEDTA·2H₂O)₃(PW₁₂O₄₀)·2H₃O (BiPW) and Na(BiHEDTA·2H₂O)₃(PMo₁₂O₄₀)·2H₃O·2H₂O (BiPMo) ethylenediamine tetraacetic acid (EDTA) have been synthesized by solution method and characterized by ultraviolet visible (UV–vis) spectroscopy, thermogravimetric-differential thermal analysis, photoluminescence, cyclic voltammetry, and single-crystal X-ray diffraction (XRD). XRD analysis reveals that BiPW and BiPMo are isostructural with 3-D architectures assembled by 2-D layer tetranuclear cation and a Keggin-type polyoxoanion. Although these two hybrids exhibit similar structures, the properties depend on the nature of polyoxoanion [PM₁₂O₄₀]^3? (M = W, Mo). Under UV irradiation, BiPW and BiPMo show fast response of reversible and irreversible photochromism, respectively. BiPW exhibits excellent photocatalytic activity in degradation of methyl orange dyes under irradiation of UV–visible light. It can be reused for at least six cycles without obvious loss of activity in the degradation experiments; BiPMo shows catalytic activity in elimination of methanol. The elimination rate of methanol reaches 56.9% when the concentration of methanol is 2.3 g·m^?3 and the flow velocity is 10 mL·min^?1 at 100 °C.     

Syntheses of Potential Degradation Products of Phenylephrine in OTC Products

Compound 1 and 2 are potential major degradants in over the counter (OTC) products containing phenylephrine HCl and dexbrompheniramine maleate or chlorpheniramine maleate. Compound 2 matches the unknown peak in the solution of stressed active and excipient and thus was identified as the correct degradation product. Whether the degradation product is racemic or chiral is not known. This article describes synthesis of both compounds. Compound 2 will be useful as an analytical standard for quantitative analysis of the major degradant in OTC products of phenylephrine HCl and dexbrompheniramine maleate or chlorpheniramine maleate.     

Mesoporous Titania-Silica nanocomposite as an effective material for the degradation of Bisphenol A under visible light

A simple and very effective method is proposed for the removal of Bisphenol A (BPA) under visible light using mesoporous TiO₂-SiO₂ nanocomposite. The material was characterized using FTIR, XRD, DRS, XPS, FESEM, HRTEM, and BET techniques. The photo degradation efficiency of TiO₂-SiO₂ compared with bare TiO₂. The effect of calcination temperature on the photo-degradation of the materials is also studied. The radical intermediates formed during the degradation of BPA were followed with different radical scavengers. The solution after reaction is subjected to TOC (Total Organic Carbon content) and LCMS analysis to determine the mineralization rate and degradation products exist in the solution. Kinetic studies were revealed that the degradation process follow pseudo first order kinetics.     

High Pressure Liquid Chromatographic Determination of Promethazine Hydrochloride in the Presence of its Thermal and Photolytic Degradation Products: A Stability Indicating Assay

Abstract

A stability indicating method has been developed for the quantitation of promethazine hydrochloride in the presence of its photolytic and thermal degradation products. Following a basic extraction with acetonitrile, promethazine is separated from its internal standard, promazine, and vehicle components by direct high performance liquid chromatography using ultraviolet detection (249 nm) and a stainless steel column 25 cm in length, 0.46 cm i.d. packed with octa-decyl silica 5μ in diameter. A linear relationship was obtained between peak height ratio (promethazine/promazine) and promethazine hydrochloride in water over the range 30–600 g/ml. The percent coefficient of variation of the assay is 0.8% and the recovery of promethazine hydrochloride from aqueous solutions is 99.7%. The photolytic degradation of promethazine hydrochloride does not follow simple first order kinetics. Potassium iodide and p-benzoquinone had a significant effect on the degradation rate of promethazine during the first 30 minutes of the photolytic degradation reaction. However, after one hour there is no apparent quenching effect on the photolytic degradation rate of promethazine hydrochloride in the presence of these quenchers.     

Stability Indicating HPLC Analysis of Dibromodulcitol in Aqueous Solutions

Abstract

A stability-indicating HPLC analytical method for the anticancer agent dibromodulcitol (DBD, Mitolactol, NSC-104800) has been developed that will completely resolve the compound from its degradation products. A 5 μm octadecylsilane analytical column was used in conjunction with a refractive index detector, with a mobile phase of 98:2 water/methanol. The limit of DBD detection was determined to be 250 ng (5 μg/ml) with a signal to noise ratio of 2:1. Intraday variation of the method, as percent relative standard deviation, was 4.37% (12.5 μg/ml) and 0.973% (250 μg/ml), and interday variation was 3.93% (250 μg/ml). Comparison with potentiometric titration of bromide after digestion of DBD with NaOH indicated that the method was more sensitive and specific than titration. The method has been used in tablet content analysis, as well as degradation studies of DBD in solution.     

A Stability Indicating Proton NMR Spectroscopic Assay Method for Succinylcholine Chloride Injections

Abstract

A simple, accurate, and specific -¹H-NMR spectroscopic method is presented for the assay of succinylcholine chloride injections. After freeze-drying the sample solution, a mixture of the residue with acetamide, serving as the internal standard, is dissolved in deuterium oxide, and the spectrum of the solution is recorded. The quantity of drug in the dosage form is calculated from the integral values for the resonance signals at ca. 2.01 ppm (acetamide) and ca. 3.27 ppm (succinylcholine chloride). The mean ± SD recovery value from synthetic formulations was 99.93 ± 0.60% (n = 10), with a corresponding CV of 0.60%. Assay values for a group of 10 commercial samples ranged from 86.1 to 100.7 (mean = 98.01)% of declared. Injection additives such as methyl paraben and benzyl alcohol did not interfere with the assays. The proposed method will also permit the simultaneous monitoring of the hydrolytic degradation of succinylcholine to its ester components.     

Determination of Propantheline Bromide in Tablet Formulations by Reverse-Phase HPLC

Abstract

The reported reverse-phase HPLC method for the determination of propantheline bromide, xanthanoic acid, xanthone, and 9-hydroxy-propantheline bromide in tablets is fast, sensitive, specific, accurate and reporoducible. Methyl xanthanoate is used as internal standard. The total elution time is 6 min. The method is stability-indicating since it can determine the degradation products. The column utilized was suplecosil LC-8 (5 micron), 250 mm × 4.6 mm i.d. The mobile phase was 0.03 M solution of ammonium acetate in acetonitrile: water: THF (60:38:2); the pH was adjusted to 4.5 with acetic acid, the detection was at 254 nm. A wavelength of 248 nm was used to quantitate xanthanoic acid and the flow rate was 1.5 mL/min. The proposed HPLC method was verified for linearity, accuracy, precision, and applicability.     

Study on CuO/Al2O3 catalytic ozone treatment of acid red B solution

A CuO/Al₂O₃ catalyst was prepared using the impregnation method. The catalytic activity of CuO/Al₂O₃ for the ozonation of acid red B (ARB) in aqueous solution was studied, the chemical oxygen demand (COD) removal rate was an indicator for catalytic activity evaluation. The effects of initial ARB concentration, solution pH, and different oxidative degradation systems on oxidative degradation of ARB solution were studied. The CuO/Al₂O₃ catalyst was characterized using X‐ray diffractometry (XRD), N₂ adsorption desorption test, X‐ray photoelectron spectroscopy (XPS), and zero‐point charge (pH_zpc). The results show that copper species on the carrier were in the form of CuO and highly dispersed on the carrier. CuO can increase the alkalinity of the Al₂O₃ surface, and the CuO/Al₂O₃ catalyst facilitates the decomposition of O₃ into ·OH, which was beneficial for the catalytic O₃ oxidation degradation reaction. With the increase of the initial concentration of simulated wastewater, the CuO/Al₂O₃ catalytic reaction still has a high COD removal rate. Alkaline solution was of benefit to catalyze the degradation of ARB solution. When the ARB solution pH = 8.93, the degradation reaction was carried out for 40 min, the COD removal rate reached 83.2%. The degradation reaction was dominated by the hydroxyl radical (·OH) reaction.     

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%.     

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.