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Development and validation of smart spectrophotometric-chemometric methods for the simultaneous determination of chlorpheniramine maleate and etilefrine hydrochloride in bulk powder and in dosage form combinations
Abstract
This paper describes threesensitive, accurate and precise chemometricspectrophotometricmethods for the simultaneous determination of chlorpheniramine maleate (CPM) and etilefrine hydrochloride (ETF)in bulk powder and capsules without prior separation. Multivariate calibration chemometric methods are proposed for simultaneous determination of CPMandETF. The chemometric methods applied are classical least squares (CLS),principal component regression (PCR) and partial least squares (PLS). These approaches aresuccessfully applied to quantify both drugs using the information included in the absorption spectra of appropriate solutions.In these multivariatemethods, calibration sets of standard samples composed of different mixtures of CPMand ETFhave been designed. The methods were validated according to the International Conference on Harmonization (ICH) guidelines. The specificity of the proposed methods was tested using laboratory-prepared mixtures. The developed methods were successfully applied for the determination of CPM and ETF in bulk powder and dosage form combination.
... CH was determined in presence of pseudoephedrine hydrochloride, dextromethorphan hydrochloride [6], phenyl propanolamine hydrochloride [8], dexamethasone and parabens [9], emetine hydrochloride [11], acetaminophen and phenylephrine hydrochloride [12], paracetamol and caffeine [13], codeine, phenylephrine hydrochloride and acetaminophen [20]. For the time being only one report was found on the direct determination of binary mixture of ET and CH through multivariate chemometric methods [10]. However no report could be found on the analysis of mixture of the cited drugs by HPLC. ...
... The suggested procedures were used for the direct estimation of ET and CH in Balkis capsules and syrups and the results obtained were contrasted with those obtained upon application of reference method [10] as illustrated in Table 3. Statistical analysis of the Fig. 5. HPLC chromatographic separation of ET (20 mg mL À1 ) and CH (20 mg mL À1 ). obtained results using F-and t-tests shows that there is no remarkable differences at 95% confidence level. ...
... Tabulated value for chemometric method (n ¼ 4 for both chemometric and reported methods** [10]) at 95% confidence limit; t ¼ 2.45 and F ¼ 9.28. *Tabulated value for HPLC method (n ¼ 3 for both HPLC and reported methods** [10]) at 95% confidence limit; t ¼ t ¼ 2.78 and F ¼ 19.00. a Reference[10]. ...
Simple, sensitive and reliable spectro-chemometric and high performance liquid chromatography (HPLC) methods were developed for simultaneous determination of binary mixture of etilefrine hydrochloride and chlorpheniramine maleate without prior separation in their bulk drugs and dosage forms. The spectro-chemometric methods used are, derivative spectrophotometry, derivative ratio, and isosbestic point methods. The HPLC method involves the use of reversed-phase separation mode using eluant of pH 3.5, consisted of phosphate buffer/acetonitrile (30:70 v/v) and Zorbax ODS column. All variables influencing the spectrophotometric and HPLC methods were carefully investigated and optimized. The developed methods were evaluated according to United State Pharmacopeia (USP) and International Conference of Harmonization (ICH) rules. The current methods were successfully implemented for direct the determination of these drugs in their trade pharmaceutical formulations. The obtained results were contrasted with those calculated after application of reference method. The data obtained from both methods were statistically analyzed by F-and t-tests. The results of such study showed excellent agreement in respect to the accuracy and precision of the suggested and reference methods.
... CH was determined in presence of pseudoephedrine hydrochloride, dextromethorphan hydrochloride [6], phenyl propanolamine hydrochloride [8], dexamethasone and parabens [9], emetine hydrochloride [11], acetaminophen and phenylephrine hydrochloride [12], paracetamol and caffeine [13], codeine, phenylephrine hydrochloride and acetaminophen [20]. For the time being only one report was found on the direct determination of binary mixture of ET and CH through multivariate chemometric methods [10]. However no report could be found on the analysis of mixture of the cited drugs by HPLC. ...
... The suggested procedures were used for the direct estimation of ET and CH in Balkis capsules and syrups and the results obtained were contrasted with those obtained upon application of reference method [10] as illustrated in Table 3. Statistical analysis of the Fig. 5. HPLC chromatographic separation of ET (20 mg mL À1 ) and CH (20 mg mL À1 ). obtained results using F-and t-tests shows that there is no remarkable differences at 95% confidence level. ...
... Tabulated value for chemometric method (n ¼ 4 for both chemometric and reported methods** [10]) at 95% confidence limit; t ¼ 2.45 and F ¼ 9.28. *Tabulated value for HPLC method (n ¼ 3 for both HPLC and reported methods** [10]) at 95% confidence limit; t ¼ t ¼ 2.78 and F ¼ 19.00. a Reference[10]. ...
... Developing non-chromatographic procedure is rather essential for pharmaceutical industry to reduce organic solvents and energy consumption associated with liquid chromatography. Statistical methods, such as the usual Multivariate Regression (MR), Partial Least Squares Regression (PLSR), Principle Component Regression (PCR) and Artificial Neural Networks (ANN), are effectively tested to replace laborious liquid chromatography [1][2][3][4][5][6][7][8][9][10][11][12][13]. These methods are inverse calibration techniques where concentrations are modelled as a function of absorbance values calculated as A = − log 10 R, where R represents the reflectance. ...
... Points 5 and 22 are regression outliers causing problem for model fitting. Points 2,9,14,19,21 are, on the other hand, potential orthogonal outliers with very large orthogonal distances. None of the observations seem to be influential. ...
Statistical methods are effectively used in evaluation of
pharmaceutical formulations instead of laborious liquid chromatography. However, Signal overlapping, nonlinearity, multicollinearity and presence of outliers deteriorate the performance of statistical methods. The Partial Least Squares Regression (PLSR) is a very popular method in quantification of high dimensional spectrally overlapped drug formulations. The SIMPLS is the mostly used PLSR algorithm, but it is highly sensitive to outliers that also effects the diagnostics. In this paper, we propose new robust multivariate diagnostics to identify outliers, influential observations and points causing non-normality for a PLSR model. We study performances of the proposed diagnostics on two every-day use highly overlapping drug systems: Paracetamol-Caffeine and Doxylamine Succinate-Pyridoxine Hydrochloride.
... It is used for the treatment of hypotensive states [2a]. Different techniques were reported for the determination of etilefrine hydrochloride including: spectrophotometry [3][4][5][6][7], spectro flourimetry [8] and HPLC [9]. . It is a direct-acting sympathomimetic with mainly beta-adrenergic activity and a selective action on beta2 receptors (a beta2 agonist). ...
A simple and sensitive method was developed for spectrophotometric determination of etilefrine hydrochloride, salbutamol sulphate and tiemonium methyl sulphate in pure form and in their pharmaceutical formulations. The method was based on reduction of gold solution to gold nanoparticles by the studied drugs in presence of sodium dodecyl sulphate as stabilising agent. Gold nanoparticles (Au NPs) showed a new absorption band at 530 nm that was used for quantitative determination of the cited drugs. Different variables were examined and optimised in the experiment as gold solution concentration, type of buffer, suitable pH, stabilising agent, order of addition, time and temperature of the reaction. Under optimum conditions, the calibration curves were linear with concentration ranges of 3.0-20.0, 5.0-18.0 and 2.0-26.0 μg/mL for etilefrine Hydrochloride, salbutamol sulphate and tiemonium methyl sulphate respectively. The method was applied successfully to determine the studied drugs in pure form and in their pharmaceutical dosage forms, exhibiting good reproducibility and accuracy. © 2017 Magda Mohamed Ayad, Hisham Ezzat Abdellatef, Mervat Mohamed Hosny, and Naglaa Abdel-Sattar Kabil.
... It is used for the treatment of hypotensive states [2]. Different techniques were reported for the determination of etilefrine hydrochloride including: spectrophotometry [3][4][5][6], spectro flourimetry [7], automated sequential injection spectro photometry [8], Flow-injection spectrophotometry [9], flow-injection chemiluminometric assay [10] and HPLC [11]. ...
Objective: The aim of this work was to evaluate a simple, sensitive, effective and validated procedure for the determination of etilefrine hydrochloride, fenoterol hydrobromide, salbutamol sulphate and estradiol valerate. Methods: In this study the method based on the ability of the cited drugs to reduce Ag + ions to silver nanoparticles (Ag-NPs) in the presence of polyvinyl pyrrolidone (PVP) as a stabilizing agent producing very intense surface plasmon resonance peak of Ag-NPs (λmax = 417-425 nm). The plasmon absorbance of the Ag-NPs allows the quantitative spectrophotometric detection of the cited drugs. Results: The calibration curves were linear with concentrations range of 0.4-0.8, 0.1-0.9, 0.8-2 and 1.6-9.6 µg/ml for the cited drugs. Apparent molar absorptivity, detection and quantitative limits were calculated. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented; also the proposed method was applied for the determination of estradiol valerate in human urine samples. Conclusion: The extracellular synthesis of nanoparticles was fast and eco-friendly; moreover, the method doesn't require various elaborate treatments and tedious extraction procedures.
Simple, Accurate, selective and sensitive UV spectrophotometric methods have been developed and validated for determination of etilefrine hydrochloride in presence of its oxidative degradation product without preliminary separation. These methods include ratio subtraction, absorbance subtraction and amplitude modulation method, These methods were based on extension region of the degradate All the proposed methods were validated and successfully applied for determination of Effortil® 5 mg tablets. The obtained results were statistically compared with those of the reported method by applying t-test and F-test at 95% confidence level and no significant difference was observed regarding accuracy and precision.
A simple, sensitive, specific and accurate stability indicating HPLC method was developed for the determination of etilefrine hydrochloride (ETF) in presence of its oxidative degradate. Computational and theoretical studies were done electronically and geometrically to investigate the affinity of ETF and its oxidative degradate to the stationary phase. The analysis was carried out on an ODS SUPELCO C18 (25 cm X 4.6 mm, 5 μm particle size) using a mobile phase consisting of [0.1M phosphate buffer, pH 4: acetonitrile (30:70, v/v)]. The analysis was performed at ambient temperature with a flow rate of 1 mL/min and UV detection at 220 nm. The proposed method can selectively analyzes the drug in presence of up to 80% of its oxidative degradate with mean recovery ± RSD % of 99.54±0.503. The proposed method was extensively validated according to the ICH guidelines and used for estimation of ETF in tablets and the obtained results were statistically compared with those of the reported method by applying t-test and F-test at 95% confidence level and no significant difference was observed regarding accuracy and precision.
A simple, precise, and accurate method is developed and validated for the analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column (5 μm, 125 × 4.6 mm inner diameter) using a mobile phase consisting of methanol/ammonium dihydrogen phosphate buffer (90:10, v/v) at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, robustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r (2) of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r (2) of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r (2) of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r (2) of 0.991. The average recovery of the method is 99.7%, 98.6%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged.
2-Furfuraldehyde, 5-hydroxymethylfurfuraldehyde and malonaldehyde are known to react with 2-thiobarbituric acid when heated in an acidic medium. A study of the influence of several chemical and physico-chemical variables on the reaction was undertaken. The products of reaction show high absorption in the visible spectral region with several degrees of overlapping. The resolution of ternary mixtures of these compounds was accomplished by several chemometric approaches. A comparative study of the results obtained for simultaneous determinations in mixtures by using derivative spectrophotometry and partial least-squares analysis is presented. The multi-wavelength factor analysis-based method is demonstrated to be the method of choice for the multi-component analysis of ternary mixtures of these compounds.
Four methods have been developed for the simultaneous determination of phenylephrine hydrochloride and chlorpheniramine maleate without previous separation. In the first method both drugs are determined using first derivative UV spectrophotometry, with zero-crossing measurement. The second method depends on first derivative of the ratios spectra. The third method describes the use of multivariate spectrophotometric calibration for the simultaneous determination of the analyzed binary mixture where the resolution is accomplished by using partial least squares (PLS) regression analysis. In the fourth method (HPLC), a reversed-phase column and a mobile phase of methanol:water:acetonitrile (80:12:8 v/v/v/) at 0.9 ml/min flow rate have been used to separate both drugs with a UV detection at 270 nm. All the proposed methods are extensively validated. They have the advantage to be economic and time saving. All the described methods can be readily utilized for analysis of pharmaceutical formulations. The results obtained using the proposed methods are statistically analyzed and compared with some reported methods
Objectives: The aim of the present work is to develop a rapid and simple method for the simultaneous determination of amlodipine besylate and atorvastatin calcium mixture by two different methods. First, Multivariate calibration methods using preprocessing to enhance results in case of presence of any interference in samples. Second, RP-HPLC method for achieving a good separation of the mixture with accepted system suitability parameters with using design of experiment in the robustness study according to Plackett-Burman design. Methods: The method is based on the spectrophotometric measurements of the drugs in the range of 200-400 nm together with multivariate calibration methods. Resolution of the binary mixture under investigation has been accomplished mainly by using partial least squares (PLS) and principal component regression (PCR). The proposed RP-HPLC method utilizes a YMC-pack pro C18 ODS-A (25 cm x 4.6 mm, 5 μm) column, at room temperature, optimum mobile phase consisted of methanol and 0.01 M sodium dihydrogen phosphate buffer (75:25, v/v), pH adjusted to 3.5 with orthophosphoric acid solution. The flow rate was monitored at 1.2 ml/min, and UV detection at 239 nm. Results: The recovery percentage for amlodipine besylate and atorvastatin calcium in tablets dosage form were found to be in PLS method (98.98 ± 0.85, 99.68 ± 1.35), PCR method (99.16 ± 0.75, 99.60 ± 1.40) and RP-HPLC method (98.82 ± 0.62, 101.19 ± 0.69), respectively. Conclusion: The methods were validated as per ICH guidelines. All the results obtained were found to be within the acceptable limits. The methods were successful to estimate amlodipine besylate and atorvastatin calcium in bulk powder and pharmaceutical preparation Caduet®.
Two multivariate calibration methods, including principal component regression (PCR) and partial least square (PLS), have been used for the determination of rosuvastatin in the presence of its oxidative degradation products. The PCR and PLS techniques are useful in spectral analysis due to the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry, thus a great improvement in the precision and predictive abilities of these multivariate calibrations is observed. A calibration set was constructed for the mixture and the best model was used for the prediction of the concentration of the selected drug. The proposed procedures were applied successfully in the determination of rosuvastatin in laboratory-prepared mixtures and in commercial preparations. Rosuvastatin was analyzed with mean accuracies 99.93 ± 0.866 and 99.99±0.645 using the PCR and PLS methods respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed procedures were found to be rapid and simple and required no preliminary separation. They can therefore be used for the routine analysis of rosuvastatin in quality-control laboratories.
The application of Principal Component Analysis (PCA) for resolving coeluted substances in doping control analysis was examined. PCA was applied on two GC/MS data sets. Firstly, on a urine sample spiked with a mixture of four control substances (methylphenidate, pethidine, caffeine and pipradrol) and secondly, on a real urine sample containing an etilefrine derivative and an artifact (BHT antioxidant), which were coeluted in the same GC peak. In both the cases clear full spectra of various component substances were extracted from the mixture spectra. The time of GC/MS analysis was significantly reduced. PCA was used in both the cases as an exploratory method of data analysis.
A quantitative procedure for the determination of dapsone [80-08-0], I, in authentic mixtures and tablets, II, has been developed using the PMR spectroscopy. The comparison of the proposed PMR method with the official assays of the B.P. 1980 was achieved, and the results were statistically evaluated. The PMR determination is fairly accurate, more precise and providing advantageous traits regarding the simplicity and the rapidity of the method as well as the specificity of the technique in identifying and testing the purity of the compound.
Multilevel experiments are common in chemistry, especially in calibration and mixture problems. This paper presents designs for l = 2–5 different concentration levels and l2 corresponding experiments. The importance of orthogonality between successive factors is discussed. It is shown that up to 12 mutually orthogonal factors can be generated for a five-level design. Methods of generating designs are generalised. The designs are restricted to first-order (linear) models, typical of most instrumental calibration experiments.
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 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.
An effort has been made to assess the potential utility of derivative spectrometry for the quantitative analysis of mixtures. Using a numerical simulation method based on pairs of overlapping Gaussian bands, we have determined the systematic and random errors of measurement methods based on the 0th, 1st, and 2nd derivatives of a number of band pairs of different height ratio, width ratio, and separation. Derivative methods were found to give the lowest total errors in most of the cases studied.
The quantitative prediction abilities of four multivariate calibration methods for spectral analyses are compared by using extensive Monte Carlo simulations. The calibration methods compared include inverse least-squares (ILS), classical least-squares (CLS), partial least-squares (PLS), and principal component regression (PCR) methods. ILS is a frequency-limited method while the latter three are capable of full-spectrum calibration. The simulations were performed assuming Beer's law holds and that spectral measurement errors and concentration errors associated with the reference method are normally distributed. Eight different factors that could affect the relative performance of the calibration methods were varied in a two-level, eight-factor experimental design in order to evaluate their effect on the prediction abilities of the four methods. It is found that each of the three full-spectrum methods has its range of superior performance. The frequency-limited ILS method was never the best method, although in the presence of relatively large concentration errors it sometimes yields comparable analysis precision to the full-spectrum methods for the major spectral component. The importance of each factor in the absolute and relative performances of the four methods is compared.
Dipyridamole (Dp) selective PVC mcmbrane based on dipyridamolium phosphotungstate ( Dp-PTA). dipyridamolium tetraphenylborate
(Dp-TPB) and a mixture of both (Dp-PTA/TPB) were prepared. The electrodes displayed a linear response over the concentration range
6.3 x 1 .0 x lo-’ mol dm--3 dipyridamole hydrochloride (DpCI). The working pH ranges of the above electrodes were 2.0-7.5,2.0-7.5
and 2.0--7.0 and their isothermal coefficients were 0.00096,0.00010 and 0.00144 VI’C, respectively. The electrodes showed good selectivity
to DpCl with respect to many inorganic cations, sugars and amino acids. Potentiometric titration and standard additions methods were
used to determine DpCl in pure solutions and in pharmaceutical preparations with high accuracy and precision.
It has been shown that Chlorpheniramine maleate (CPM) increases chemiluminescence intensity of bis-(2,4,6-trichlorophenyl)oxalate (TCPO) with hydrogen peroxide in the presence of biphenylquinoxaline as a fluorophore. In this work, the effect of CPM on the intensity of chemiluminescence (CL) in the system of (TCPO–sodium salicylate–fluorophore–hydrogen peroxide) was investigated. The fall and rise rates constants were also studied. A pooled-intermediate model was used for determining the kinetics parameters of CL with and without CPM. Results indicated that addition of CMP to this system increases the fall rate constant and decreases the rise rate constant. Results also specified that there is a linear relationship between CPA concentration and chemiluminescence intensity in the range 0.66–21.5 μg/ml. Detection limit 0.18 μg/ml and the relative standard deviation (RSD) <7% was obtained. This work is introduced as a new method for the determination of CMP.Highlights► The present study convincingly shows the enhancement of chemiluminescence intensity of peroxyoxalte chemiluminescence system (TCPO- H2O2- sodium salicylate- fluorescer) in the presence of chlorpheniramine maleate. ► Results also introduced a reliable method for determination of chlorpheniramine using peroxyoxalte chemiluminescence system. ► A pooled-intermediate model was used for determination the kinetics parameters of chemiluminescence with and without chlorpheniramine maleate. ► Results also specified that there is a linear relationship between chlorpheniramine maleate concentration and chemiluminescence intensity.
Mixtures of food colorants, containing tartrazine, sunset yellow, ponceau 4R, amaranth and brilliant blue, were simultaneously analyzed with spectrophotometry without previous chemical separation. The data obtained from experiments were processed by chemometric approaches, such as classical least squares (CLS), principal component regression (PCR), partial least squares (PLS) and iterative target transformation factor analysis (ITTFA), using the normal absorbance spectra and first- and second-derivative absorbance spectra. Sixteen mixtures of colorants with five-combination were evaluated and the results obtained by the application of the different chemometric approaches were discussed and compared. It was found that ITTFA often afforded better precision than those of CLS, PCR and PLS, and calibrations based on first-derivative data provided some advantages for all these four methods. The proposed method was applied satisfactorily to the determination of colorants in several commercial food products.
The effect of detection chip geometry on chemiluminescence (CL) signal intensity of tris(1,10-phenanthroline)-ruthenium(II) peroxydisulphate system for analysis of chlorpheniramine maleate (CPM) in pharmaceutical formulations was investigated. It was observed that the design of the detection chip is very crucial and can play an important role in enhancing the CL signal intensity in this system. The CL signal intensity was enhanced 250% when a teardrop micromixer chip was used, compared to the commonly used serpentine chip geometry. The study was conducted using a multi-chip device. In this device, chip 1 was used to prepare and pump the reagent mixture, whereas chip 3 was used for pumping the sample. The two chips were connected to the teardrop chip (2) via silica capillary where detection took place. Non-linear regression curve fitting of the calibration data revealed that the calibration curves are best described by third order polynomial equation with excellent correlation coefficients (R(2)=0.9998) for the concentration range 7.69 × 10(-8) to 5.12 ×1 0(-5)mol L(-1). A linear response is also observed over the range 7.69 × 10(-8) to 1.28 × 10(-5)mol L(-1) (R(2)=0.9996) and the detection limit was found to be 5.49 × 10(-8)mol L(-1). The device was successfully used for the analysis of CPM in tablets and a multi-component cough syrup. Results were reproducible with relative standard deviation (RSD) of 0.6-1.1%.
Resolution of binary mixtures of paracetamol, phenylephrine hydrochloride and chlorpheniramine maleate with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable, principal component regression and hybrid linear analysis. Data of analysis were obtained from UV-vis spectra of the above compounds. The method of central composite design was used in the ranges of 1-15 mg L(-1) for both calibration and validation sets. The models refinement procedure and their validation were performed by cross-validation. Figures of merit such as selectivity, sensitivity, analytical sensitivity and limit of detection were determined for all three compounds. The procedure was successfully applied to simultaneous determination of the above compounds in pharmaceutical tablets.
Three multivariate calibration methods, partial least squares (PLS-1 and PLS-2) and principal component regression (PCR), were applied to the simultaneous determination of three flavour enhancers (inosine 5'-monophosphate, guanosine 5'-monophosphate and monosodium glutamate), in mixtures by ultraviolet/visible absorption spectrophotometry. The absorption and first- and second-derivative absorption spectra of the ternary mixtures were used to perform the optimization of the calibration matrices by the PLS and PCR methods. The results obtained by the application of the different chemometric approaches are discussed and compared. No significant advantages were found for the prior differentiation step. The proposed method was applied satisfactorily to the determination of inosine 5'-monophosphate and guanosine 5'-monophosphate in several food preparations, in the presence of monosodium glutamate.
The present paper describes a simple, accurate and precise reversed phase HPLC method for rapid and simultaneous quantification of codeine phosphate, ephedrine HCl and chlorpheniramine maleate in a cough-cold syrup formulation. Separations were carried out on a Zorbax XDB C8 column (150 x 4.6 mm ID), 5 microm particle size. A gradient elution system was developed using varying percentages of two mobile phases: methanol-glacial acetic acid-triethylamine (980:15:6 v/v) and water-glacial acetic acid-triethylamine (980:15:6 v/v). The elution of the analytes was achieved in less than 7 min with a flow rate of 1.5 ml/min. Detection was by UV absorbance at a wavelength of 254 nm. Quantification of the components in actual syrup formulations was calculated against the responses of freshly prepared external standard solutions. The method was validated and met all analysis requirements of quality assurance and quality control recommended by FDA of the USA.
A simple, fast, economical and automated sequential injection spectrophotometric method for the determination of etilefrine hydrochloride is developed. The method is based on the condensation reaction of etilefrine hydrochloride with 4-aminoantipyrine in the presence of alkaline potassium hexacyanoferrate and the absorbance of the colored product measured at 503 nm. Aspiration order, flow rate, reaction coil diameter, reaction coil length, concentration of 4-aminoantipyrine and potassium ferricyanide, as well as aspiration volume of reagents and sample has been optimized. Using these optimized parameters, a linear relationship between the relative peak height and concentration was obtained in the range 1-20 mg l(-1). The detection limit (as 3sigma value) was 0.1 mg l(-1) and precision was 2.7% and 1.5% at 1 and 2 mg l(-1), respectively. This method is superior over previously reported ones in terms of linear range, short analysis time, high sample throughput, excellent reagent economy and minimum waste generation.
An easy, rapid and simple nonaqueous capillary electrophoresis (NACE) method was developed for the identification and determination of four basic nitrogenous compounds, i.e. pseudoephedrine (PE), dextromethorphan (DXM), diphenhydramine (DHM) and chlorpheniramine (CLP). The most suitable running buffer was composed of 40 mM ammonium acetate, 10% acetonitrile (ACN) in methanol with a fused-silica capillary column (47 cm x 75 microm i.d.), 25 kV applied voltage and 25 degrees C capillary temperature. The calibration curves revealed linear relationships between the peak area for each analyte and its concentration (correlation coefficients: 0.9993 for PE, 0.9971 for DXM, 0.9991 for DHM, and 0.9995 for CLP, respectively). The relative standard deviations of the migration time and peak area of the four compounds were 0.37, 3.90, 0.73 and 0.68, and 2.80, 3.50, 1.60 and 3.70%, respectively. The method was successfully applied to determine the four compounds in five cold medicines, the recoveries of the four constituents ranging between 91 and 109%.