Validated Sensitive Spectrophotometric methods for Determination of Carvedilol and Nebivolol HCl in dosage forms.

A simple, sensitive and rapid spectrophotometric methods were developed and validated for the determination of two antihypertensive drugs namely, carvedilol and nebivolol hydrochloride in pure form and pharmaceutical formulations. Method (I) is based on the formation of a binary complex between the studied drugs and eosin Y in presence of tween 80 at (pH 3.0).The formed complex exhibited maximum absorption at 545 nm for carvedilol and 543 nm for nebivolol. The concentration plots were rectilinear over concentration range of 0.5-5 and 1-7 µg/mL with lower detection limits of 0.09 and 0.11µg/mL and lower quantitation limits of 0.28 and 0 .34 µg/mL for carvedilol and nebivolol respectively. Method (II) is based on the reaction of studied drugs through their secondary amino groups with 2, 4-dinitrofluorobenzene (DNFB) at pH 8 to form yellow colored reaction products peaking at 383 nm and 390 nm for carvedilol and nebivolol, respectively. The absorbance-concentration plots were rectilinear over the concentration ranges of 5-30 and 4-28 µg/ mLwith the lower detection limits of 0.48 and 0.51 µg/mL and the lower quantitation limits of 1.45 and 1.54 µg/mL for cavredilol and nebivolol respectively. The different experimental parameters affecting the development and stability of the formed complex and reaction products were carefully studied and optimized for both methods. Both methods were successfully applied for determination of the studied drugs in their dosage forms

Simultaneous determination of sulpiride and mebeverine by HPLC method using fluorescence detection: application to real human plasma

A new simple, rapid and sensitive reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of sulpiride (SUL) and mebeverine Hydrochloride (MEB) in the presence of their impurities and degradation products. The separation of these compounds was achieved within 6 min on a 250 mm, 4.6 mm i.d., 5 m particle size Waters®-C18 column using isocractic mobile phase containing a mixture of acetonitrile and 0.01 M dihydrogenphosphate buffer (45:55) at pH = 4.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence-detection at excitation 300 nm and emission at 365 nm. The concentration-response relationship was linear over a concentration range of 10- 100 ng/mL for both MEB and SUL with a limit of detection 0.73 ng/mL and 0.85 ng/mL for MEB and SUL respectively. The proposed method was successfully applied for the analysis of both MEB and SUL in bulk with average recoveries of 100.22 ± 0.757% and 99.96 ± 0.625% respectively, and in commercial tablets with average recoveries of 100.04 ± 0.93% and 100.03 ± 0.376% for MEB and SUL respectively. The proposed method was successfully applied to the determination of MEB metabolite (veratic acid) in real plasma simultaneously with SUL. The mean% recoveries (n = 3) for both MEB metabolite (veratic acid) and SUL were 100.36 ± 2.92 and 99.06 ± 2.11 for spiked human plasma respectively. For real human plasma, the mean% recoveries (n = 3) were and respectively

Development and validation of stability indicating method for determination of sertraline following ICH guidlines and its determination in pharmaceuticals and biological fluids

<p>Abstract</p> <p>Background</p> <p>Sertraline is a well known antidepressant drug which belongs to a class called selective serotonin reuptake inhibitor. Most published methods do not enable studying the stability of this drug in different stress conditions.</p> <p>Results</p> <p>Two new methods were developed for the determination of sertraline (SER). Both methods are based on coupling with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.8 and measuring the reaction product spectrophotometrically at 395 nm (Method I) or spectrofluorimetrically at 530 nm upon excitation at 480 nm (Method II). The response-concentration plots were rectilinear over the range 2-24 μg/mL and 0.25-5 μg/mL for methods I and II respectively with LOD of 0.18 μg/mL and 0.07 μg/mL, and LOQ of 0.56 μg/mL and 0.21 μg/mL for methods I and II, respectively.</p> <p>Conclusion</p> <p>Both methods were applied to the analysis of commercial tablets and the results were in good agreement with those obtained using a reference method. The fluorimetric method was further applied to the in vivo determination of SER in human plasma. A proposal of the reaction pathway was presented. The spectrophotometric method was extended to stability study of SER. The drug was exposed to alkaline, acidic, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of oxidative degradation of the drug. The apparent first order rate constant and t_1/2of the degradation reaction were determined.</p

Synchronous fluorescence spectrofluorimetric method for the simultaneous determination of metoprolol and felodipine in combined pharmaceutical preparation

A rapid, simple and sensitive synchronous specrtofluorimetric method has been developed for the simultaneous analysis of binary mixture of metoprolol (MTP) and felodipine (FDP). The method is based upon measurement of the synchronous fluorescence intensity of the two drugs at Δλ of 70 nm in aqueous solution. The different experimental parameters affecting the synchronous fluorescence intensities of the two drugs were carefully studied and optimized. The fluorescence intensity-concentration plots were rectilinear over the ranges of 0.5-10 μg/mL and 0.2-2 μg/mL for MTP and FDP, respectively. The limits of detection were 0.11 and 0.02 μg/mL and quantification limits were 0.32 and 0.06 μg/mL for MTP and FDP, respectively. The proposed method was successfully applied for the determination of the two compounds in their commercial tablets and the results obtained were favorably compared to those obtained with a comparison method

Development and validation of a repharsed phase- HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma

<p>Abstract</p> <p>Background</p> <p>Rosiglitazone (ROZ) and glimepiride (GLM) are antidiabetic agents used in the treatment of type 2 diabetes mellitus. A survey of the literature reveals that only one spectrophotometric method has been reported for the simultaneous determination of ROS and GLM in pharmaceutical preparations. However the reported method suffers from the low sensitivity, for this reason, our target was to develop a simple sensitive HPLC method for the simultaneous determination of ROZ and GLM in their combined dosage forms and plasma.</p> <p>Results</p> <p>A simple reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Rosiglitazone (ROS) and Glimepiride (GLM) in combined dosage forms and human plasma. The separation was achieved using a 150 mm × 4.6 mm i.d., 5 μm particle size Symmetry^®C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer of pH 5 (60: 40, V/V) was pumped at a flow rate of 1 mL/min. UV detection was performed at 235 nm using nicardipine as an internal standard. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of Avandaryl™ tablets. The chromatographic analysis time was approximately 7 min per sample with complete resolution of ROS (t_R= 3.7 min.), GLM (t_R= 4.66 min.), and nicardipine (t_R, 6.37 min). Validation studieswas performed according to ICH Guidelines revealed that the proposed method is specific, rapid, reliable and reproducible. The calibration plots were linear over the concentration ranges 0.10-25 μg/mL and 0.125-12.5 μg/mL with LOD of 0.04 μg/mL for both compounds and limits of quantification 0.13 and 0.11 μg/mL for ROS and GLM respectively.</p> <p>Conclusion</p> <p>The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in Avandaryl™ tablets were 100.88 ± 1.14 and 100.31 ± 1.93 for ROS and GLM respectively. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The interference likely to be introduced from some co-administered drugs such as glibenclamide, gliclazide, metformine, pioglitazone and nateglinide was investigated.</p

Utility of certain nucleophilic aromatic substitution reactions for the assay of pregabalin in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin (PG) is an anticonvulsant, analgesic and anxiolytic drug. A survey of the literature reveals that all the reported spectrophotometric methods are either don't offer high sensitivity, need tedious extraction procedures, recommend the measurement of absorbance in the near UV region where interference most probably occurs and/or use non specific reagent that don't offer suitable linearity range.</p> <p>Results</p> <p>Two new sensitive and simple spectrophotometric methods were developed for determination of pregabalin (PG) in capsules. Method (I) is based on the reaction of PG with 1,2-naphthoquinone-4-sulphonate sodium (NQS), yielding an orange colored product that was measured at 473 nm. Method (II) is based on the reaction of the drug with 2,4-dinitrofluorobenzene (DNFB) producing a yellow product measured at 373 nm. The different experimental parameters affecting the development and stability of the reaction product in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-25 and 0.5-8 μg mL^-1for methods (I) and (II) respectively. The lower detection limits (LOD) were 0.15 and 0.13 μg mL^-1and the lower quantitation limits (LOQ) were 0.46 and 0.4 μg mL^-1for methods (I) and (II) respectively.</p> <p>Conclusion</p> <p>The developed methods were successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recoveries of PG in its capsule were 99.11 ± 0.98 and 100.11 ± 1.2 (n = 3). Statistical analysis of the results revealed good agreement with those given by the comparison method. Proposals of the reaction pathways were postulated.</p

Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

<p>Abstract</p> <p>Background</p> <p>Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form).</p> <p>Results</p> <p>A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL^-1with a lower detection limit of 5.34 × 10^-3μg mL^-1and limit of quantitation of 0.016 μg mL^-1.</p> <p>Conclusions</p> <p>The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.</p

Spectrophotometric determination of certain CNS stimulants in dosage forms and spiked human urine via derivatization with 2,4-Dinitrofluorobenzene

Abstract A new spectrophotometric method is developed for the determination of phenylpropanolamine HCl (PPA), ephedrine HCl (EPH) and pseudoephedrine HCl (PSE) in pharmaceutical preparations and spiked human urine. The method involved heat-catalyzed derivatization of the three drugs with 2,4-dinitrofluorobenzene (DNFB) producing a yellow colored product peaking at 370 nm for PPA and 380 nm for EPH and PSE, respectively. The absorbance concentration plots were rectilinear over the range of 2-20 for PPA and 1-14 μg/mL for both of EPH and PSE, respectively. The limit of detection (LOD) values were 0.20, 0.13 and 0.20 μg/mL for PPA, EPH and PSE, respectively and limit of quantitation (LOQ) values of 0.60 and 0.40 and 0.59 μg/mL for PPA, EPH and PSE, respectively. The analytical performance of the method was fully validated and the results were satisfactory. The proposed method was successfully applied to the determination of the three studied drugs in their commercial dosage forms including tablets, capsules and ampoules with good percentage recoveries. The proposed method was further applied for the determination of PSE in spiked human urine with a mean percentage recovery of 108.17 ± 1.60 for (n = 3). Statistical comparison of the results obtained with those of the comparison methods showed good agreement and proved that there was no significant difference in the accuracy and precision between the two methods. The mechanism of the reaction pathway was postulated.</p