[Show abstract][Hide abstract] ABSTRACT: Export Date: 24 April 2013, Source: Scopus, CODEN: JLCTF, :doi 10.1080/10826076.2011.615094, Language of Original Document: English, Correspondence Address: Kaufman, T.S.; Department of Organic Chemistry, National University of Rosario, Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario (S2002LRK), Argentina; email: firstname.lastname@example.org, : Chemicals/CASvalsartan, 137862-53-4, Tradenames: Prostar 210, Varian, United States, Manufacturers: Varian, United States, References: Thurmann, P.A., Valsartan: A Novel Angiotensin Type 1 Receptor Antagonist (2000) Expert Opin. Pharmacother., 1, pp. 337-350;
Journal of Liquid Chromatography & Related Technologies 01/2012; 35(8):1053-1069. · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The novel triple combination between Amlodipine (AML), Hydrochlorothiazide (HCT), and Valsartan (VAL) provides a new option for treating hypertension. The development and validation of an HPLC method for their simultaneous determination in pharmaceutical combinations, employing experimental design strategies, is reported. The drugs were separated on a C18 column at 30°C, using a 38:62 (v/v) mixture of 30 mM phosphate buffer (pH 5.5) and MeOH as mobile phase, delivered at 1.0 mL min. Detection was performed at 234 nm.Despite the wide difference in analytes’ concentrations, the method showed good linearity (r > 0.995) in the ranges 7.0–13.0 µg mL, 17.6–32.8 µg mL, and 226.2–420.2 µg mL for AML, HCT, and VAL, respectively, being specific (peak purity >0.999), accurate (bias of analyte recoveries
Journal of Liquid Chromatography & Related Technologies 11/2011; 34(19):2383-2395. · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (λ > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
Journal of pharmaceutical and biomedical analysis 08/2011; 56(1):16-22. · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A capillary zone electrophoresis method for the simultaneous determination of pridinol mesylate (PRI) and meloxicam (MEL)
employing epinastine hydrochloride and piroxicam as internal standards, was developed and optimized employing experimental
design and response surface methodologies. The separation was optimally achieved in less than 2min at 30kV in an uncoated
fused-silica capillary (41.4cm×75μm I.D.), employing an 18mmolL−1 sodium phosphate buffer solution (pH 5.90) at 25°C. Samples were injected in hydrodynamic mode (50mbar, 5s) and the analytes
were spectrophotometrically detected at 200nm. Method robustness was demonstrated by ANOVA of determinations performed under
conditions slightly different from the optimum. The method was validated regarding separation selectivity (peak purity factors>0.99),
linearity and range (PRI=17.6–31.4mgL−1; MEL=66.5–122.5mgL−1), accuracy (PRI=100.2–101.9%; MEL=98.9–100.7%) and precision. The RSD values obtained were ≤1.3% for injection repeatability
and ≤1.9% for intra-day precision. The limits of detection (1.0 and 0.9mgL−1) and quantification (3.3 and 16.5mgL−1) of PRI and MEL, respectively, were also determined. The method was successfully applied to the determination of both drugs
in three brands of tablet formulations. No statistically significant differences were observed when these results were compared
with those of a RP-HPLC method.
KeywordsCapillary zone electrophoresis–Experimental designs–Meloxicam–Pridinol
[Show abstract][Hide abstract] ABSTRACT: The development and validation of an HPLC method for the determination of pridinol and diclofenac in their combined formulations and the simultaneous limit testing of diclofenac related compound A is described. The separation was performed on a C18 column. Experimental design and response surface strategies were employed for optimizing detection wavelength (225 nm) and mobile phase composition [MeOH:2-propanol:phosphate buffer (50 mM, pH 5.5), 48:9:43 (v/v/v), 1 mL min−1], and for validation purposes. The method was successfully applied to the quality control of commercial brands of tablets and capsules. Found impurity levels were below 0.1% (LOQ = 0.02%). Stressed samples were also evaluated.
Journal of Liquid Chromatography & Related Technologies 11/2010; 33(19):1720-1732. · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association of meloxicam and pridinol is indicated for treating muscular contractures and low back pain. A dissolution test for the meloxicam-pridinol combined tablet formulation was developed and validated, using a suitable HPLC method for simultaneously quantitating both dissolved drugs. The optimized conditions include the use of USP apparatus 2 at a paddle rotation rate of 75 rpm and 900 ml of 50 mM phosphate buffer (pH= 7.5) as dissolution medium, at 37.0±0.5°. The test, which demonstrated to be robust against small changes in bath temperature, paddle rotation speed and pH of the dissolution medium, was applied to two different brands of tablets; the corresponding dissolution profiles were constructed and both brands showed to dissolve at least 75% of the drugs at the 45 min time point.
Indian Journal of Pharmaceutical Sciences 03/2010; 72(2):197-203. · 0.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A simple high performance liquid chromatographic method for the determination of process-related impurities in bulk drug of the central anticholinergic compound pridinol mesylate, has been developed and validated. Spectroscopically characterized synthetic impurities were used as standards. The chromatographic separation was optimized employing an experimental design strategy, and was achieved on a C(18) column with a mobile phase containing 50mM potassium phosphate buffer (pH 6.4), MeOH and 2-propanol (20:69:11, v/v/v), delivered at a flow rate of 1.0mLmin(-1). UV detection was performed at 245nm. The optimized method was thoroughly validated, demonstrating to be selective, when the chromatogram was recorded with a diode-array detector and peak purities were evaluated (>0.9995). The method is robust and linear (r(2)>0.99) over the range 0.05-2.5% (5-250% with regards to the 1% specification limit for both process-related impurities); it is also precise, regarding repeatability (RSD</=1.5% for all of the analytes) and intermediate precision aspects and LOQ values for the impurities are below 0.01%. Method accuracy, evidenced by low bias of the results and analyte recoveries in the range of 99.1-102.7%, was assessed at five analyte concentration levels. The usefulness of the determination was also demonstrated through the analysis of different lots of pridinol mesylate bulk substance. The results indicate that the method is suitable for the quality control of the bulk manufacturing of pridinol mesylate drug substance.
[Show abstract][Hide abstract] ABSTRACT: A simple chemometric approach to differentiate among the three crystalline polymorphs of the model drug Furosemide (FUR) in a pharmaceutical dosage form is presented. The proposed method is based on the principal component analysis with confidence regions (PCA-CR) comparison of the dissolution profiles of the test pharmaceutical formulation, and formulations containing the different polymorphs, employed as the corresponding references. For the elaboration of the references, FUR polymorphs I, II and III were prepared, characterized and compounded with the excipients found in the test commercial formulation. The dissolutions were carried out in a discriminating HCl-KCl dissolution medium (pH 2.2), and the corresponding profiles were constructed from the absorbances (274 nm) of the dissolution samples. PCA-CR was able to differentiate among the three crystalline polymorphs of FUR and to confirm the presence of polymorph I in the test sample, with 99% statistical confidence. The PCA-CR results were compared with those obtained by a bootstrap-mediated implementation of Moore and Flanner's difference factor (f(2)). The same conclusion was reached employing an f(2)-based comparison, despite its inability to differentiate between polymorphs II and III. Therefore, PCA-CR may be considered a complementary and useful tool for probing the polymorphic form present in a pharmaceutical formulation.
International Journal of Pharmaceutics 06/2009; 378(1-2):187-93. · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The stability of pridinol mesylate (PRI) was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal, as recommended by the ICH guidelines. Relevant degradation was found to take place under acidic (0.1N HCl) and photolytic (visible and long-wavelength UV-light) conditions, both yielding the product resulting from water elimination (ELI), while submission to an oxidizing environment gave the N-oxidation derivative (NOX). The standards of these degradation products were synthesized and characterized by IR, (1)H and (13)C NMR spectroscopy. A simple, sensitive and specific HPLC method was developed for the quantification of PRI, ELI and NOX in bulk drug, and the conditions were optimized by means of a statistical design strategy. The separation employs a C(18) column and a 51:9:40 (v/v/v) mixture of MeOH, 2-propanol and potassium phosphate solution (50mM, pH 6.0), as mobile phase, delivered at 1.0 ml min(-1); the analytes were detected and quantified at 220 nm. The method was validated, demonstrating to be accurate and precise (repeatability and intermediate precision levels) within the corresponding linear ranges of PRI (0.1-1.5 mg ml(-1); r=0.9983, n=18) and both impurities (0.1-1.3% relative to PRI, r=0.9996 and 0.9995 for ELI and NOX, respectively, n=18). Robustness against small modifications of pH and percentage of the aqueous mobile phase was ascertained and the limits of quantification of the analytes were also determined (0.4 and 0.5 microg ml(-1); 0.04% and 0.05% relative to PRI for ELI and NOX, respectively). Peak purity indices (>0.9997), obtained with the aid of diode-array detection, and satisfactory resolution (R(s)>2.0) between PRI and its impurities established the specificity of the determination, all these results proving the stability-indicating capability of the method. The kinetics of the degradation of PRI in acid medium was also studied, determining that this is a first-order process with regards to drug concentration, with an activation energy of 25.5 Kcal mol(-1) and a t(1/2)=10,830 h, in 0.1N HCl at 38 degrees C.
Journal of Pharmaceutical and Biomedical Analysis 09/2008; 48(4):1151-60. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A convenient new method for the simultaneous determination of losartan potassium and hydrochlorothiazide, with minimum sample pretreatment, is described. The procedure, based on the multivariate analysis of spectral data in the 220-274 nm region by the partial least squares algorithm, is linear in the concentration range 1.06-5.70 mg L(-1) for hydrochlorothiazide and 4.0-22.2 mg L(-1) for losartan. It is simple, rapid and robust, allowing accurate and precise results, with drug recovery rates of 99.3 and 100.4% and relative standard deviations of 1.7 and 1.0% obtained for hydrochlorothiazide and losartan, respectively. The method was applied to the simultaneous determination of both analytes in tablets, and it provided good results which were in statistical agreement with those provided by independent HPLC analyses of the samples. The method has also been successfully applied for the construction of drug dissolution profiles of a commercial pharmaceutical preparation containing both analytes.
Analytical and Bioanalytical Chemistry 07/2008; 391(8):2949-55. · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new approach for testing batch "similarity" through comparison of drug dissolution profiles, based on principal component analysis with the establishment of a confidence region (PCA-CR), is presented. The dissolution curves corresponding to three brands each of Furosemide and Acetaminophen tablets, taken as model drugs, were prepared by dissolution measurements at multiple pre-specified time points. Reference and test data were simultaneously subjected to PCA and pairwise comparisons between the dissolution characteristics of lots of the same and different brands were carried out. The comparisons involved plotting the weighed scores of the first two principal components of reference and test lots, while decision about "similarity" was made by checking for inclusion of more than 80% of the tablets of the test lot in the 95% confidence ellipse of the reference samples. Two published datasets were also analyzed in the same fashion and all the results were compared with information provided by the difference (f1) and similarity (f2) factor tests. Unlike the f2 criterion, the proposed method reflects variability within the individual dissolution curves, being also highly sensitive to profile (shape and size) variations. Comparison between the area enclosed by the confidence ellipses of the weighed scores plot and the region obtained from the bootstrap-calculated acceptable values of the corresponding f2 tests suggested that PCA-CR represents, in general, a more discriminating standard.
European Journal of Pharmaceutical Sciences 06/2008; 34(1):66-77. · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been developed and validated for the simultaneous determination of meloxicam and pridinol mesylate in their synthetic mixtures and combined tablet formulations. Both drugs were separated on a 250 mm x 4.6mm C18 column packed with 5 microm particles. The mobile phase, optimized through an experimental design, was a 51:9:40 (v/v/v) mixture of methanol, isopropanol and 50mM potassium phosphate buffer (pH 5.9), pumped at a flow rate of 1.0 ml min(-1). UV detection was performed at 225 nm. The method was validated in the sample concentration ranges of 33.7-61.8 mg l(-1) for meloxicam and 8.8-16.8 mg l(-1) for pridinol mesylate, where it demonstrated good linearity with r=0.9989 and 0.9987 (n=15), respectively. The assay was shown to be repeatable at concentration levels of 70%, 100% and 130%, with relative standard deviation values of 1.09% and 0.82% for meloxicam and pridinol, respectively. For independent 100% level samples, the intra-day precision was 0.4% and 1.0% while the intermediate precision was 0.7% and 1.0% for the drugs. The method demonstrated to be robust, resisting to small deliberate changes in pH, flow rate and composition (organic:aqueous ratio) of the mobile phase. The LOD values were 0.22 and 0.20 mg l(-1), while the LOQ were 1.7 and 1.1 mg l(-1), for meloxicam and pridinol, respectively. The applicability of the method was demonstrated by determining the drug content of two commercial pharmaceutical formulations, where it exhibited good performance.
Journal of Pharmaceutical and Biomedical Analysis 02/2008; 46(2):219-25. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An alternative method for the determination of fexofenadine (FEX) and pseudoephedrine (PSE) in their combined tablet formulation has been developed, employing the partial least squares (PLS) analysis of spectral data of the analytes in their pharmaceutical association. A full-factorially designed set of 16 synthetic samples was employed for calibration purposes. The calibration models were constructed with wavelengths selection, in the ultraviolet region, according to their predictive ability. These were validated internally by the leave-one-out procedure and externally, employing appropriate sets of validation samples. The described method was linear for both analytes, over the range 160.6-301.2 mg L(-1) for FEX (R(2)=0.9993) and between 325.6 and 610.5 mg L(-1) for PSE (R(2)=0.9992). It was accurate, exhibiting 99.8% and 99.9% drug recoveries for FEX and PSE, respectively (N=9), while in the intermediate precision experiment relative standard deviations were 1.4% for FEX and 1.2% for PSE. The contents of both analytes were assayed in commercial tablets employing this method and the results were compared with those furnished by HPLC, being in good statistical agreement. The method represents an improvement over the first derivative of spectral ratio (DSR) technique and allows high sample throughput with minimum reagent consumption and waste generation. The obtained results confirm that the method is highly suitable for its intended purpose.
Journal of Pharmaceutical and Biomedical Analysis 01/2008; 45(5):804-10. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cited By (since 1996):1, Export Date: 24 April 2013, Source: Scopus, Language of Original Document: Spanish, Correspondence Address: Kaufman, T.S.; Area Análisis de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 531, S2002LRK Rosario, Argentina; email: email@example.com, : Chemicals/CASparacetamol, 103-90-2, References: Greco, A., Ajmone-Cat, M.A., Nicolini, A., Sciulli, M.G., Minghetti, L., (2003) J. Neurosci. Res, 71, pp. 844-852;
LATIN AMERICAN JOURNAL OF PHARMACY 01/2008; 27(4):603-607. · 0.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been developed and validated for the simultaneous
determination of meloxicam and pridinol mesylate in their synthetic mixtures and combined tablet formulations. Both drugs were separated on a
250mm×4.6mm C18 column packed with 5 �m particles. The mobile phase, optimized through an experimental design, was a 51:9:40 (v/v/v)
mixture of methanol, isopropanol and 50mM potassium phosphate buffer (pH 5.9), pumped at a flow rate of 1.0 ml min−1. UV detection was
performed at 225 nm. The method was validated in the sample concentration ranges of 33.7–61.8 mg l−1 for meloxicam and 8.8–16.8 mg l−1 for
pridinol mesylate, where it demonstrated good linearity with r = 0.9989 and 0.9987 (n = 15), respectively. The assay was shown to be repeatable at
concentration levels of 70%, 100% and 130%, with relative standard deviation values of 1.09% and 0.82% for meloxicam and pridinol, respectively.
For independent 100% level samples, the intra-day precision was 0.4% and 1.0% while the intermediate precision was 0.7% and 1.0% for the
drugs. The method demonstrated to be robust, resisting to small deliberate changes in pH, flow rate and composition (organic:aqueous ratio) of the
mobile phase. The LOD values were 0.22 and 0.20 mg l−1, while the LOQ were 1.7 and 1.1 mg l−1, for meloxicam and pridinol, respectively. The
applicability of the method was demonstrated by determining the drug content of two commercial pharmaceutical formulations, where it exhibited
Journal of Pharmaceutical and Biomedical Analysis 01/2008; 48:1151. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two new analytical methods have been developed as convenient and useful alternatives for simultaneous determination of hydrochlorothiazide (HCT) and propranolol hydrochloride (PRO) in pharmaceutical formulations. The methods are based on the first derivative of ratio spectra (DRS) and on partial least squares (PLS) analysis of the ultraviolet absorption spectra of the samples in the 250-350-nm region. The methods were calibrated between 8.7 and 16.0 mg L(-1) for HCT and between 14.0 and 51.5 mg L(-1) for PRO. An asymmetric full-factorial design and wavelength selection (277-294 nm for HCT and 297-319 for PRO) were used for the PLS method and signal intensities at 276 and 322 nm were used in the DRS method for HCT and PRO, respectively. Performance characteristics of the analytical methods were evaluated by use of validation samples and both methods showed to be accurate and precise, furnishing near quantitative analyte recoveries (100.4 and 99.3% for HCT and PRO by use of PLS) and relative standard deviations below 2%. For PLS the lower limits of quantification were 0.37 and 0.66 mg L(-1) for HCT and PRO, respectively, whereas for DRS they were 1.15 and 3.05 mg L(-1) for HCT and PRO, respectively. The methods were used for quantification of HCT and PRO in synthetic mixtures and in two commercial tablet preparations containing different proportions of the analytes. The results of the drug content assay and the tablet dissolution test were in statistical agreement (p < 0.05) with those furnished by the official procedures of the USP 29. Preparation of dissolution profiles of the combined tablet formulations was also performed with the aid of the proposed methods. The methods are easy to apply, use relatively simple equipment, require minimum sample pre-treatment, enable high sample throughput, and generate less solvent waste than other procedures.
Analytical and Bioanalytical Chemistry 12/2006; 386(7-8):2239-44. · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Six 3H-spiro[benzofuran-2,1'-cyclohexane] derivatives were synthesized from naturally occurring filifolinol, and their classical complement pathway inhibitory activity was determined. IC(50) values of the most potent compounds were comparable to the activity of the natural complement inhibitor K76-COOH and some synthetic tricyclic analogs of it.
[Show abstract][Hide abstract] ABSTRACT: A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.
Analytical and Bioanalytical Chemistry 09/2005; 382(7):1711-4. · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Different chemometric methods such as classical least squares (CLS), principal components regression (PCR) and partial least squares with one dependent variable (PLS-1) applied on UV spectral data (0 D) and on their first derivatives (1 D) were evaluated for the simultaneous quantification of samples containing mixtures of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate. Their performances were compared by means of ANOVA tests, which evidenced that 0 D-PCR, 0D-PLS-1, 1D-PCR, 1D-PLS-1, were reproducible and gave statistically similar results, while 0 D-CLS and 1D-CLS displayed higher variances than the former and failed to comply with the Levene's variance homogeneity test at different stages of the method comparison and validation process. The four statistically equivalent procedures were successfully applied to the analysis of synthetic samples with two to four analytes and to commercial tablet preparations containing amiloride hydrochloride and hydrochlorothiazide alone or in association with atenolol or timolol maleate.
Journal of Pharmaceutical and Biomedical Analysis 03/2004; 34(2):305-14. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Resolution of binary mixtures of atenolol (ATE) and chlorthalidone (CTD) with minimum sample pre-treatment and without analyte separation has been successfully achieved, using a new and rapid method based on partial least squares (PLS1) analysis of UV spectral data. The simultaneous determination of both analytes was possible by PLS1 processing of sample absorbances between 255 and 300 nm for ATE and evaluation of absorbances in the 253-268 nm region for CTD. The mean recoveries for synthetic samples were 100.3 +/- 1.0% and 100.7 +/- 0.7% for ATE and CTD, respectively. Application of the proposed method to two commercial tablet preparations in the content uniformity test showed them to contain 103.5 +/- 0.8% and 104.9 +/- 1.8% ATE respectively, as well as 103.4 +/- 1.2% and 104.5 +/- 2.2% CTD. Use of this method also allowed the elaboration of dissolution profiles of the drugs in two commercial combined formulation products, through the simultaneous determination of both drugs during the dissolution test. At the dissolution time of 45 min specified by USP XXIV, both pharmaceutical formulations complied with the test.
Analytical and Bioanalytical Chemistry 01/2004; 377(7-8):1159-64. · 3.66 Impact Factor