Manal Eid

Stability‐Indicating HPLC Method for the Determination of Quetiapine: Application to Tablets and Human Plasma

Abstract A stability‐indicating reversed‐phase high performance liquid chromatographic method was developed for the analysis of the antipsychotic drug quetiapine. Quetiapine was determined in presence of two of its degradation products; quetiapine N‐oxide and quetiapine lactam. The analysis was carried out using a 250 mm×4.6 mm i.d., 5 µm particle size Zorbax SB‐Phenyl column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer (50∶50) at pH=5.5 was pumped at a flow rate of 1 mL/min with UV detection at 254 nm. The method showed good linearity in the range of 0.08–20 µg/mL with limit of detection (S/N=3) 0.03 µg/mL (3.3×10−8 M). The suggested method was successfully applied for the analysis of quetiapine in bulk, tablets, and human plasma with average recoveries of 99.96±1.25%, 101.37±0.481%, and 100.82±1.53%, respectively. The proposed method was also applied for the determination of quetiapine in the presence of some co‐administered drugs as clomipramine, carbamazepine, and fluconazole.

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.

Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations

Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS) in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides) producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm.Method (IIA) describes quantitative fluorescence quenching of eosin upon addition of the studied drug where the decrease in the fluorescence intensity was directly proportional to the concentration of ebastine; the fluorescence quenching was measured at 553 nm after excitation at 457 nm. This method was extended to (Method IIB) to apply first and second derivative synchronous spectrofluorimetric method (FDSFS & SDSFS) for the simultaneous analysis of EBS in presence of its alkaline, acidic, and UV degradation products.The proposed methods were successfully applied for the determination of the studied compound in its dosage forms. The results obtained were in good agreement with those obtained by a comparison method. Both methods were utilized to investigate the kinetics of the degradation of the drug.

Stability-indicating micelle-enhanced spectrofluorimetric method for determination of loratadine and desloratadine in dosage forms.

A highly sensitive and simple spectrofluorimetric method was developed for the determination of loratadine (LRT) and desloratadine (DSL) in their pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behaviour of LRT and DSL in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution of acetate buffer of pH 4.5, the fluorescence intensities of both LRT and DSL were greatly enhanced (240%) in the presence of SDS. The fluorescence intensity was measured at 438 nm after excitation at 290 nm for both drugs. The fluorescence-concentration plots were rectilinear over the range 0.05-2.0 µg/mL for both LRT and DSL, with lower detection limits of 5.13 × 10(-3) and 6.35 × 10(-3) µg/mL for LRT and DSL, respectively. The method was successfully applied to the analysis of the two drugs in their commercial tablets, capsules and syrups, and the results were in good agreement with those obtained with the official or comparison methods. The proposed method is specific for the determination of LRT in the presence of other co-formulated drugs, such as pseudoephedrine. The application of the proposed method was extended to stability studies of LRT and DSL after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines.

Polarographic determination of some penicillins through nitrosation

Direct current and differential pulse polarography DPP were used for the determination of three penicillins, namely, ampicillin, benzylpenicillin and carbenicillin, in pure form and in their dosage forms. The method is based upon treatment of penicillins with nitrous acid followed by polarographic measurement of the produced derivatives polarographically. The nitroso derivatives formed exhibited reduction waves over the whole pH range in Britton-Robinson buffers. The waves were characterized as being diffusion-controlled and free from adsorption phenomena. The current-concentration plots were rectilinear over the concentration range 8-200 and 2-160 micrograms ml-1 for DCt and DPP, respectively, for all the studied compounds. The proposed method was further applied to determine penicillins in pharmaceutical preparations, and the results obtained were in good agreement with those given by the companies.

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

BackgroundAlendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Pagets disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.ResultsThree simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beers law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.ConclusionThe proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.Graphical abstract

Validated stability indicating liquid chromatographic determination of ebastine in pharmaceuticals after pre column derivatization: Application to tablets and content uniformity testing

An accurate, simple, sensitive and selective reversed phase liquid chromatographic method has been developed for the determination of ebastine in its pharmaceutical preparations. The proposed method depends on the complexation ability of the studied drug with Zn2+ ions. Reversed phase chromatography was conducted using an ODS C18 (150 × 4.6 mm id) stainless steel column at ambient temperature with UV-detection at 260 nm. A mobile phase containing 0.025%w/v Zn2+ in a mixture of (acetonitril/methanol; 1/4) and Britton Robinson buffer (65:35, v/v) adjusted to pH 4.2, has been used for the determination of ebastine at a flow rate of 1 ml/min. The calibration curve was rectilinear over the concentration range of 0.3 - 6.0 μg/ml with a detection limit (LOD) of 0.13 μg/ml, and quantification limit (LOQ) of 0.26 μg/ml. The proposed method was successfully applied for the analysis of ebastine in its dosage forms, the obtained results were favorably compared with those obtained by a comparison method. Furthermore, content uniformity testing of the studied pharmaceutical formulations was also conducted. The composition of the complex as well as its stability constant was also investigated. Moreover, the proposed method was found to be a stability indicating one and was utilized to investigate the kinetics of alkaline and ultraviolet induced degradation of the drug. The first-order rate constant and half life of the degradation products were calculated.

Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y.

A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 μg/mL and 1-12 μg/mL with limits of detection of 0.1 μg/mL and 0.3 μg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets.

Stability-Indicating Micellar Liquid Chromatographic Method for the Determination of Clopidogrel. Application to Tablets and Content Uniformity Testing

Abstract A simple, stability-indicating, reversed-phase micellar liquid chromatographic method was developed for the analysis of the antiplatelet drug clopidogrel. Clopidogrel was determined in presence of its carboxylic acid degradation product, namely; SR26334. The analysis was carried out using a 150 mm × 4.6 mm i.d., 5 µm particle size Nucleodur MN-C18 column. The Mobile phase used was a solution containing 0.15 M sodium dodecyl sulphate and 10% n-propanol and 0.3% triethylamine in 0.02 M phosphoric acid at pH = 3.0 pumped at a flow rate of 1 mL/min with UV-detection at 235 nm. The method showed good linearity in the range of 1-20 µg/mL with limit of detection (S/N = 3) 0.06 µg/mL (1.86 × 10−7 M). The suggested method was successfully applied for the analysis of clopidogrel in bulk and in commercial tablets with average recoveries of 99.67% ± 0.94%, and 100.27 ± 0.89%, respectively. The results were favorably compared to those obtained by a reference method. The proposed method was successfully applied to the content uniformity testing of tablets. The proposed method was also applied for the determination of clopidogrel in the presence of its co-administered drug, acetyl salicylic acid, with application to synthetic mixtures and prepared tablets.

Micellar HPLC and Derivative Spectrophotometric Methods for the Simultaneous Determination of Fluconazole and Tinidazole in Pharmaceuticals and Biological Fluids

Micellar high-performance liquid chromatography (HPLC) and first-derivative ultraviolet spectrophotometry were used to simultaneously determine fluconazole (FLZ) and tinidazole (TNZ) in combined pharmaceutical dosage forms. The derivative procedure is based on the linear relationship between the drug concentration and the first derivative amplitudes at 220 and 288 nm for FLZ and TNZ, respectively. The calibration graphs were linear in the range of 1.5-9.0 µg/mL for FLZ and 10.0-60.0 µg/mL for TNZ. Furthermore, an HPLC procedure with ultraviolet detection at 210 nm was developed. For the HPLC procedure, good chromatographic separation was achieved using an ODS C18 column (250 × 4.6 mm i.d.). The mobile phase containing 0.15M sodium dodecyl sulphate, 0.3% triethylamine and 12% n-propanol in 0.02M orthophosphoric acid at pH 5.5 was pumped at a flow rate of 1 mL/min. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 1.5-30.0 and 10.0-200.0 µg/mL, with limits of detection of 0.36 and 2.70 µg/mL and limits of quantification of 1.1 and 8.2 µg/mL for FLZ and TNZ, respectively. The suggested methods were successfully applied for the simultaneous analysis of the drugs in their laboratory prepared mixture, co-formulated tablet and single dosage forms. Moreover the second method was also extended to the determination of the drugs in biological fluids.