淀粉铁的制备及其铁含量的测定

目的 改进淀粉铁的制备方法，建立淀粉铁中铁含量的测定方法。方法 用邻二氮菲铁分光光度法测定了淀粉铁产品中铁(Ⅲ)的含量。对淀粉铁制备过程中的工艺参数(pH值、保温温度和原料比例)进行了探讨，并对淀粉铁在水溶液、酸溶液和碱溶液中的稳定性进行了考察。结果 发现在pH3的条件下，淀粉的酸水解液与铁(Ⅲ)能形成比较稳定的络合物，其水溶性较好。结论 本工艺路线方法简单，原料易得，适合工业化生产。     

Quantitative analysis of bucillamine and its pharmaceutical formulation using FT-IR spectroscopy

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of bucillamine. Conventional KBr-spectra and DRIFTS spectra were compared for best determination of active substance in its tablet formulation. Two chemometric approaches, partial least squares (PLS) and principal component regression (PCR+) methods were used in data processing. Similar results were obtained with both chemometric methods.     

FT-IR spectrophotometric analysis of dehydroepiandrosterone and its pharmaceutical formulation

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of dehydropeiandrosterone. Conventional KBr spectra and KBr + 2.0 mg microcrystalline cellulose (MCC) spectra were compared for best determination of active substance in drug formulation. Two chemometric approaches, partial least-squares (PLS) and principal component regression (PCR+) methods were used in data processing. The best results were obtained with PCR+ method.     

Simultaneous spectrophotometric determination of diclofenac potassium and methocarbamol in binary mixture using chemometric techniques and artificial neural networks

In this study, the simultaneous determination of diclofenac potassium (DP) and methocarbamol (MT) by chemometric approaches and artificial neural networks using UV spectrophotometry has been reported as a simple alternative to using separate models for each component. Three chemometric techniques-classical least-squares (CLS), principal component regression (PCR), and partial least-squares (PLS)-along with radial basis function-artificial neural network (RBF-ANN) were prepared by using the synthetic mixtures containing the two drugs in methanol. A set of synthetic mixtures of DP and MT was evaluated and the results obtained by the application of these methods were discussed and compared. In CLS, PCR, and PLS, the absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 260-310 nm in the intervals with Δλ = 0.2 nm in their zero-order spectra. Then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of DP and MT in their mixtures. In RBF-ANN, the input layer consisting of 251 neurons, 9 neurons in the hidden layer, and 2 output neurons were found appropriate for the simultaneous determination of DP and MT. The accuracy and the precision of the four methods have been determined and they have been validated by analyzing synthetic mixtures containing the two drugs. The proposed methods were successfully applied to a pharmaceutical formulation containing the examined drugs.     

Simultaneous spectrophotometric determination of paracetamol, phenylephrine and chlropheniramine in pharmaceuticals using chemometric approaches

Background and the purpose of the study

The linear multivariate calibration models such as principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) due to the mathematical simplicity and physical or chemical interpretability are sufficient and generally preferred method for analysis of multicomponent drugs. In this study, simultaneous determination of paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using chemometric methods and UV spectrophotometry is reported as a simple alternative technique.

Material and methods

Principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) were used for chemometric analyses of data obtained from the spectra of paracetamol, phenylephrine and chlorpheniramine between wavelengths of 200 to 400 nm at several concentrations within their linear ranges. The analytical performance of these chemometric methods were characterized by relative prediction errors and recoveries (%) and compared with each other.

Results

PCR, PLS1 and PLS2 were successfully applied to a tablet formulation, with no interference from excipients as indicated by the recovery. However, the PLS1 shows better results due to its flexibility and mathematical principals.

Conclusion

The proposed methods are simple and rapid requiring no separation step, and can be easily used as an alternative in the quality control of drugs.     

Determination of diosmin in pharmaceutical formulations using Fourier transform infrared spectrophotometry

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of diosmin in different pharmaceutical drugs. Conventional KBr-spectra were compared for best determination of active substance in commercial preparations. The Beer–Lambert law and two chemometric approaches, partial least squares (PLS) and principal component regression (PCR+) methods, were tried in data processing.     

A new technique for spectrophotometric determination of pseudoephedrine and guaifenesin in syrup and synthetic mixture

The accuracy in predicting different chemometric methods was compared when applied on ordinary UV spectra and first order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS1) and two dependent variables (PLS2) were applied on spectral data of pharmaceutical formula containing pseudoephedrine (PDP) and guaifenesin (GFN). The ability to derivative in resolved overlapping spectra chloropheniramine maleate was evaluated when multivariate methods are adopted for analysis of two component mixtures without using any chemical pretreatment. The chemometrics models were tested on an external validation dataset and finally applied to the analysis of pharmaceuticals. Significant advantages were found in analysis of the real samples when the calibration models from derivative spectra were used. It should also be mentioned that the proposed method is a simple and rapid way requiring no preliminary separation steps and can be used easily for the analysis of these compounds, especially in quality control laboratories.     

Spectrophotometric determination of Fe(II) and Zn(II) in the pharmaceutical multivitamin preparations with microelements

3-mercapto-5-(3,4-dihydroxyphenylazo-1')-1,2,4-triazole (METRIAP), 3-mercapto-5-(2,4-dihydroxy-3-carboxyphenylazo-1)-1,2,4-triazole (METRIAREZ-gamma) and 2-mercapto-5-(2,4-dihydroxy-5-carboxyphenylazol-)-1,3,4-thiadiazole (METIDAREZ-beta), reagents synthesized in the Department of Medicinal Chemistry of Medical University in Lublin, have been used to determine Fe(II) and Zn(II) in Materna, Centrum, H-Pantoten pharmaceutical multivitamin preparations, containing other trace elements. Zn (II) with METRIAREZ-gamma at pH=7.35, and Fe(II) with METRIAP and METIDAREZ-beta at pH=10.30 or 7.40 constitute soluble in H2O colourful chelate compound at a mole ratio of 1:2 and 1:3, respectively. Volume stability constant of Fe(II) and Zn(II) complexes is equal to log K(METRIAP-Fe(II)) = 16.46; log K(METRIAREZ-beta-Fe(II)) = 14.253; log K(METRIAREZ-gammaZn(II)) = 11.47. Fe(III) and Zn(II) solutions were obtained by wet mineralisation of Materna, Centrum and H-Pantoten preparations with concentrated H2SO4 and 30% H2O2 added. Spectrophotometric determination was carried out in an aqueous-methanolic solution environment. Statistically evaluated results were compared with the results of the AAS (atomic absorption spectrophotometry) determination method. Advantages of the Fe(II) and Zn(II) determination method are its precision RSD = 0.23%-2.09% and repeatability as well as the possibility of Fe(II) determination without the necessity of masking or separating other trace elements.     

Spectrophotometric quantitative determination of cilazapril and hydrochlorothiazide in tablets by chemometric methods

Four chemometric methods were applied to simultaneous determination of cilazapril and hydrochlorothiazide in tablets. Classical least-square (CLS), inverse least-square (ILS), principal component regression (PCR) and partial least-squares (PLS) methods do not need any priori graphical treatment of the overlapping spectra of two drugs in a mixture. For all chemometric calibrations a concentration set of the random mixture consisting of the two drugs in 0.1 M HCI and methanol (1:1) was prepared. The absorbance data in the UV-Vis spectra were measured for the 15 wavelength points (from 222 to 276 nm) in the spectral region 210-290 nm considering the intervals of deltalambda = 4 nm. The calibration of the investigated methods involves only absorbance and concentration data matrices. The developed calibrations were tested for the synthetic mixtures consisting of two drugs and using the Maple V software the chemometric calculations were performed. The results of the methods were compared each other as well as with HPLC method and a good agreement was found.     

Dissolution and assaying of multicomponent tablets by chemometric methods using computer-aided spectrophotometer

Dissolution of three component tablets containing paracetamol (APAP), propyphenazone (PP), and caffeine (CAF) was carried out by USP paddle method. Three chemometric methods; inverse least square (ILS), principal component regression (PCR) and partial least squares (PLS) were applied to simultaneous assay of APAP, PP and CAF in tablets. The PCR, PLS and ILS methods were applied to simultaneous dissolution APAP, PP and CAF in tablets using a double beam UV-Vis spectrophotometer without any chemical separation and any graphical treatment of the overlapping spectra of three drugs. Twenty two mixture solutions in different concentrations were prepared in simulated gastric juice (SGJ, USP) for the chemometric calibrations as training set. The absorbance data matrix was obtained by measuring the absorbance at 14 wavelength points (from 222.5 to 292.5 nm) with the intervals of 5 nm (Deltalambda=5 nm) in the spectral region between 200 and 310 nm. Training set and absorbance data were used for the calibrations of chemometric methods. The developed calibrations were tested for the previously prepared solutions of mixture of three drugs for the validation of the assay method. The chemometric calculations were performed by using the 'MAPLE VRSQUO; software. The results of three chemometric methods were statistically compared with each other. These chemometric calibrations were successfully applied to the content uniformity and dissolution of the multicomponent tablets without any separation procedure. The synthetic mixtures of three drugs were used for the validity of the calibrations. Means recoveries (percent) and relative standard deviation of PLS, PCR and ILS methods were found to be 100.1+/-0.6, 101.4+/-1.6 and 100.1+/-0.6 for APAP; 100.9+/-3.2, 102.0+/-3.3 and 100.9+/-3.2 for PP; 99.9+/-3.5, 101.6+/-3.3 and 99.9+/-3.2 for CAF, respectively. Dissolution profiles of three component tablets were performed. More than 95% of drugs were dissolved within 15 min. All of the three-chemometric methods in this study can be satisfactorily used for the quantitative analysis and for dissolutions test of multicomponent dosage form.     

HPLC and chemometric methods for the simultaneous determination of cyproheptadine hydrochloride, multivitamins, and sorbic acid

Three methods are presented for the simultaneous determination of cyproheptadine hydrochloride (CP), thiamine hydrochloride (B1), riboflavin-5-phosphate sodium dihydrate (B2), nicotinamide (B3), pyridoxine hydrochloride (B6), and sorbic acid (SO). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase, RP 18 column. Elution was carried out with 0.1% methanolic hexane sulphonic acid sodium salt (solvent A) and 0.01 M phosphate buffer containing 0.1% hexane sulphonic acid sodium salt, adjusted to an apparent pH of 2.7 (solvent B). Gradient HPLC was used with the solvent ratio changed from 20:80 to 70:30 (over 9 min), then to 80:20 (over 11 min) for solvent A:B, respectively. Quantitation was achieved with UV detection at 220 and 288 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS). These approaches were successfully applied to quantify each drug in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 250-290 nm with the intervals Deltalambda = 0.4 nm at 100 wavelengths. The chemometric methods do not require any separation step. The three methods were successfully applied to a pharmaceutical formulation and the results were compared with each other.     

Spectophotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods

Spectrophotometric simultaneous determination of hydrochlorothiazide and spironolactone in tablets was performed by classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS). The methods of the chemometric analysis do not require sample pretreatment procedure. A training set of 25 standard mixture containing both drugs was prepared in the concentration range of 2-20 mug/ml according to mixture design. The multivarate calibrations were obtained by measuring the zero-order and first-derivative absorbances at 15 points from 220 to 290 nm using the training set. The validation of the multivariate methods was realised by analysing the synthetic mixtures of hydrochlorothiazide and spironolactone. The result obtained on the synthetic mixture and tablets were statistically compared by the one-way ANOVA test. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of hydrochlorothiazide and spironolactone in the pharmaceutical tablet formulation.     

Fourier transform infrared investigation of non-heme Fe(III) and Fe(II) decomposition of artemisinin and of a simplified trioxane alcohol.

Fourier transform infrared spectra are reported for the Fe(III)- and Fe(II)-mediated activation of the antimalarial agents artemisinin 1 and its simplified synthetic analogue, trioxane alcohol 2. By monitoring the frequencies of the newly established marker lines in the FTIR spectra, the products of the Fe(II) and Fe(III) reactions have been characterized. In both reactions, artemisinin is activated giving a product mixture of a ring-contracted tetrahydrofuran acetatal 3, C(4)-hydroxy deoxyartemisinin 4, and deoxyartemisinin 5. These data illustrate that the oxidation state of the iron places no restrictions on the endoperoxide reduction mechanism. The FTIR difference (light - dark) spectra indicate that the endoperoxide moiety of artemisinin is photolabile and that the resulted products have the same vibrational characteristics as those observed in the reactions with Fe(II) and Fe(III). The use of 18O-18O enriched endoperoxide in 2 has allowed us to identify two oxygen sensitive modes in the reactions with Fe(II). The reduction of the peroxide bond by Fe(II) in trioxane alcohol 2 follows both the C-C cleavage and 1,5-H shift pathways and produces a ring-contracted tetrahydrofuran acetal 6 which is converted to tetrahydrofuran aldehyde 7 and C(4)-hydroxy deoxytrioxane alcohol 8, respectively. The cleavage of the O-O bond in 1 and 2 by iron and the ability to correlate vibrational properties of the reaction products with structural properties of the isolated products suggest that infrared spectroscopy is an appropriate tool to study the mode of action of antimalarial endoperoxides.     

Hypothesis testing for the validation of the kinetic spectrophotometric methods for the determination of lansoprazole in bulk and drug formulations via Fe(III) and Zn(II) chelates

Point and interval hypothesis tests performed to validate two simple and economical, kinetic spectrophotometric methods for the assay of lansoprazole are described. The methods are based on the formation of chelate complex of the drug with Fe(III) and Zn(II). The reaction is followed spectrophotometrically by measuring the rate of change of absorbance of coloured chelates of the drug with Fe(III) and Zn(II) at 445 and 510 nm, respectively. The stoichiometric ratio of lansoprazole to Fe(III) and Zn(II) complexes were found to be 1:1 and 2:1, respectively. The initial‐rate and fixed‐time methods are adopted for determination of drug concentrations. The calibration graphs are linear in the range 50–200 µg ml⁻¹ (initial‐rate method), 20–180 µg ml⁻¹ (fixed‐time method) for lansoprazole‐Fe(III) complex and 120–300 (initial‐rate method), and 90–210 µg ml⁻¹ (fixed‐time method) for lansoprazole‐Zn(II) complex. The inter‐day and intra‐day precision data showed good accuracy and precision of the proposed procedure for analysis of lansoprazole. The point and interval hypothesis tests indicate that the proposed procedures are not biased. Copyright © 2010 John Wiley & Sons, Ltd.     

Determination of astemizole, terfenadine and flunarizine hydrochloride by ternary complex formation with eosin and lead(II)

A simple and sensitive spectrophotometric method has been established for the determination of astemizole(I), terfenadine(II) and flunarizine hydrochloride(III) based on ternary complex formation with eosin and lead(II). The method does not involve solvent extraction. The colour of the produced complex is measured at 547.5 nm for (I) and (III), while (II) is measured at 540.7 nm. Appropriate conditions were established for the colour reaction and for the eosin: Pb(II): drug ratio to obtain maximum sensitivity. Under the proposed conditions, the method is applicable over concentration range of 4.1–37.6, 11.8–47.2 and 2.4–19.1 μg ml⁻¹ with mean percentage recovery of 99.20±0.63, 99.76±0.39 and 99.60±0.47% for (I), (II) and (III), respectively. The suggested method was applied for determination of (I), (II) and (III) in pharmaceutical preparations. Through the use of a non-ionic surfactant (methylcellulose), prior extraction of the drugs was unnecessary. The results obtained demonstrated that the method is equally accurate, precise and reproducible as the official or reported methods. For the purpose of enhancing the sensitivity, a fluorescence quenching method for determination of the studied drugs via ternary complex formation was also investigated. The detection limit for the studied drugs (I), (II) and (III) was 0.94–7.1 μg ml⁻¹ with mean percentage recovery of 99.84±0.29, 99.24±0.36 and 99.34±0.26%, respectively. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by official or reference methods. Unlike other reported ion-pair techniques, the suggested methods have the advantage of being applicable for the determination of the three drugs in their pharmaceutical dosage forms without prior extraction. They are recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical techniques are of great importance.     

Simultaneous determination of trimethoprim and sulphamethoxazole in veterinary formulations by chromatographic multivariate methods

A comparative chromatographic study was developed for the simultaneous quantitative resolution of trimethoprim (TMP) and sulphamethoxazole (SMX) in veterinary formulations. Multi-wavelength chromatograms were recorded by using diode array detector (DAD) system at the five-wavelength set consisting of 220, 230, 240, 250 and 260 nm. In the first step, five different calibration equations at the above wavelengths for each drug were obtained by using the relationship between concentration and peak area. These calibration graphs were used for the quantitative evaluation of TMP and SMX in samples. These single-wavelength applications were called traditional LC method. In the second step, principal component regression (PCR) and partial least-squares (PLS) calibrations were applied to the above mentioned multi-wavelength chromatograms. The amount of two investigated drugs in samples was determined by the constructed PCR and PLS calibrations. The experimental results obtained from each single-wavelength calibration graph were compared with those obtained by the chemometric approaches and chromatographic multivariate approaches give successful results more than traditional LC method.     

Application of some chemometric methods in conventional and derivative spectrophotometric analysis of acetaminophen and ascorbic acid

The multivariate methods, principal component regression (PCR) and partial least squares (PLS) were tested as a calibration procedure for simultaneous ultraviolet spectrophotometric determination of acetaminophen (AC) and ascorbic acid (AA). Determination of these compounds is important because of their pharmacotherapeutic advantages. Due to spectral overlapping of AC and AA, PCR and PLS were used for construction of the calibration sets. The concentration linear range of AC and AA were 1.5–24.2 and 1.8–21.1 µg mL^?1 respectively. The absorption spectra were recorded from 215–310 nm. The minimum root mean square error of prediction (RMSEP) was 1.3507 and 0.4088 for AC and AA, by PLS, 0.7525 and 0.4015 by PCR in original data and 0.9454 and 0.2875, by PLS and 1.0386 and 0.4000 by PCR in derivative data. The procedure allows the simultaneous determination of AC and AA in synthetic mixtures and real sample solutions made up from pharmaceutical products, human serum and urine. Copyright © 2010 John Wiley & Sons, Ltd.     

Process analytical technology (PAT): quantification approaches in terahertz spectroscopy for pharmaceutical application

Terahertz (THz) spectroscopy and chemometric analysis of resultant absorption spectra in the 30-500 cm(-1) range has been applied to perform quantitative determination of both active ingredient and excipient concentrations of tablets. Tests were performed on a series of tablets composed of various concentrations and processes of theophylline formulated with lactose, magnesium stearate, starch or Avicel, and as a function of tablet hardness. Transmission spectra of polyethylene pellets derived from each of the samples were analyzed using three approaches. Spectral superposition method was used as an indirect measure to examine whether and when the interaction among various pharmaceutical components and the tableting history could be considered insignificant for quantification purpose. Spectral characteristic peak method was able to correlate peak maxima with correction for tablets having the same hardness. Multivariate analysis (PCR and PLS 1) was capable of correlating THz spectra with tablet concentrations. The predicted concentrations of independent samples using multivariate models agreed well with nominal concentrations. The best correlations were obtained using multivariate analysis. With these studies, the advantage of using multivariate approach was demonstrated for process analytical technology (PAT) application. Further, the feasibility of integrating THz spectroscopy and chemometrics for the purpose of quantifying pharmaceutical tablet concentrations was demonstrated.     

Differential effects of Cu(II) and Fe(III) on the binding of omeprazole and pantoprazole to bovine serum albumin: toxic effect of metal ions on drugs

The interaction between omeprazole or pantoprazole and bovine serum albumin (BSA) has been investigated in the absence and presence of Cu(II) or Fe(III) by means of fluorescence spectroscopy. The fluorescence intensity of BSA decreased remarkably with slight blue shifts by adding omeprazole or pantoprazole. Similar blue shifts and fluorescence shape with larger quenching extent of BSA were observed with increasing concentrations of omeprazole or pantoprazole in the presence of Cu(II) or Fe(III). The presence of Cu(II) and Fe(III) increased the affinities of omeprazole with BSA about 12.0% and 3.9%, while the presence of Cu(II) decreased the affinity of pantoprazole with BSA about 25.7%, and the presence of Fe(III) improved the affinity of pantoprazole with BSA about 16.3%. The changeable affinity and increased binding distance in the presence of metal ions may result from a noncompetitive binding in different albumin sites. The results indicated that the structures of omeprazole or pantoprazole and kinds of metal ions together affected the binding interaction with BSA, which may have relevant consequence in rationalizing dosage for patients with gastric ulcer.