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An efficient, economic and high yielding method was described for the synthesis of baclofen (BAC) pharmacopoeial impurities (impurity A and impurity B) which can be used for gram-scale synthesis. Furthermore, a novel ecofriendly thin-layer chromatographic TLC-densitometric method was established and validated for the determination of BAC and its synthesized impurities. The developed TLC-densitometric method is based on the chromatographic separation using TLC plates (60 F 254 ) using a green mobile phase of ethyl acetate-methanol-ammonia solution, 33% (8:2:0.1, by volume) with UV scanning at 220 nm. The proposed method was validated with respect to International Conference on Harmonization guidelines. The validated method was successfully applied for determination of BAC in pure form and in its commercial dosage form. Additionally, the greenness profile of the developed method was evaluated and compared with those of the reported chromatographic methods. The developed method was found to be superior to the published methods, being environmentally benign., (© 2019 John Wiley & Sons, Ltd.)

Ascorbic acid (ASC), paracetamol (PAR) and guaifenesin (GUF) are co-formulated together as analgesic and expectorant effervescent powder. This work describes a selective stability indicating HPTLC-densitometric method which is the first developed stability indicating one for chromatographic separation of the three studied drugs in presence of paracetamol toxic impurity [4-aminophenol (4-AP)] and guaifenesin related substance [impurity, (guaiacol) (GUC)]. The chromatographic separation was carried out on HPTLC 60F254 plates using chloroform-acetone-trifluoroacetic acid (6.5:3.5:0.30, by volume) as a developing system with UV detection at 254 nm. Factors affecting chromatographic separation have been optimized and good separation was obtained between the studied components where (ASC Rf = 0.05, 4-AP Rf = 0.12, GUF Rf = 0.24, PAR Rf = 0.41 and GUC Rf = 0.56). Method validation has been performed according to ICH guidelines and linearity was achieved in the range of 0.4-2.4, 0.4-2.8 and 4-15 μg/band for ASC, PAR and GUF, respectively. In order to evaluate the developed method it was applied for determination of the cited drugs in G.C.Mol® effervescent powder and the obtained results were statistically compared with those obtained by applying the reported HPLC method using Student's t- and F-tests where no significant difference was observed. The developed method has the advantages over the reported HPLC one of being more sensitive and selective which permit its application in quality control analysis of the cited their in presence of drug impurities.

Two accurate, selective, and precise chromatographic methods, namely TLC-densitometric and reversed-phase (RP)-HPLC, were developed and validated for the simultaneous determination of nifuroxazide (NIF) and its four synthesized impurities, which are also reported to be its related substances in the range of 10-100 μg/band and 10-100 μg/mL for NIF in the TLC and RP-HPLC methods, respectively. The developed TLC-densitometric method depended on the separation and quantitation of the studied components on silica gel 60 F254 TLC plates. Ethyl acetate-acetone-methanol-ammonia (85 + 25 + 5 + 0.5, v/v/v/v) was used as the developing system, and the separated bands were UV-scanned at 230 nm. On the other hand, the developed RP-HPLC method depended on chromatographic separation using a C8 column at 25°C and an aqueous solution of 0.1% sodium lauryl sulfate-acetonitrile as the mobile phase delivered according to the gradient elution program. Factors affecting the developed methods were studied and optimized. Also, method validation was carried out according to International Conference on Harmonization guidelines. The proposed methods were successfully applied for the determination of the studied drug in its bulk powder and in its pharmaceutical formulation. The developed methods showed no significant difference when compared with the reported RP-HPLC one. Their advantage is being the first stability-indicating methods for NIF and its genotoxic impurities.

Two sensitive, accurate and precise chromatographic methods mentioned as TLC-densitometric method and RP-HPLC-DAD method, were developed and validated for the simultaneous determination of mefenamic acid (MEF) and its two toxic impurities, benzoic acid (BA) and 2,3-dimethylaniline (DMA). In the proposed TLC-densitometric method a developing system consisting of chloroform:acetone:acetic acid:ammonia solution(70:30:2:2, v/v/v/v) was used, TLC aluminum plates 60 F254 was used as a stationary phase and the separated bands were UV-scanned at 225 nm. While the proposed RP-HPLC-DAD method depended on chromatographic separation on C18 column using 0.05 M KH2PO4 buffer: acetonitrile (40:60, v/v) as a mobile phase at constant flow rate of 1 mL/min with UV detection at 225 nm. Linear relationships were obtained in the ranges of 0.3-2, 0.3-2 and 0.3-1.8 μg/band (for TLC-densitometric method) and in the ranges of 7-50, 10-50 and 7-50 μg/mL (for HPLC-DAD method) for MEF, BA and DMA, respectively. Factors affecting the developed methods have been studied and optimized. Moreover ,the proposed methods were successfully applied for determination of the studied drug in its pharmaceutical dosage form. The methods showed no significance difference when compared with the reported method using F-test and Student's-t test. The low of detection and quantization limits of the proposed methods get them suitable for quality control and stability studies of MEF in pharmaceutical formulation. The developed methods have advantages of being more selective and sensitive than the published methods., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Newly established TLC-densitometric and RP-HPLC methods were developed and validated for the simultaneous determination of Piracetam (PIR) and Vincamine (VINC) in their pharmaceutical formulation and in the presence of PIR and VINC degradation products, PD and VD, respectively. The proposed TLC-densitometric method is based on the separation and quantitation of the studied components using a developing system that consists of chloroform-methanol-glacial acetic acid-triethylamine (8 + 2 + 0.1 + 0.1, v/v/v/v) on TLC silica gel 60 F254 plates, followed by densitometric scanning at 230 nm. On the other hand, the developed RP-HPLC method is based on the separation of the studied components using an isocratic elution of 0.05 M KH2PO4 (containing 0.1% triethylamine adjusted to pH 3 with orthophosphoric acid)-methanol (95 + 5, v/v) on a C8 column at a flow rate of 1 mL/min with diode-array detection at 230 nm. The developed methods were validated according to International Conference on Harmonization guidelines and demonstrated good accuracy and precision. Moreover, the developed TLC-densitometric and RP-HPLC methods are suitable as stability-indicating assay methods for the simultaneous determination of PD and VD either in bulk powder or pharmaceutical formulation. The results were statistically compared with those obtained by the reported RP-HPLC method using t- and F-tests.

This work presents an accurate, sensitive and selective thin-layer chromatography-densitometry method for the simultaneous determination of diacerein in the presence of rhein, the active metabolite and hydrolytic degradation product of diacerein, and emodin, the diacerein impurity, in bulk powder and different pharmaceutical formulations. Chromatographic separation was performed on aluminum plates precoated with 60 F254 silica gel using hexane-ethyl acetate-acetic acid (60:40:0.8, by volume) as a developing system and with detection at 230 nm. The retention factor values of diacerein, rhein and emodin were 0.12, 0.44 and 0.6, respectively. The method was successfully applied for the determination of these compounds with high sensitivity; the linearity ranges were found to be 0.5-10 µg/band (for diacerein and rhein) and 0.5-7 µg/band (for emodin). The developed method was validated according to International Conference on Harmonization guidelines and was applied for the determination of diacerein in different pharmaceutical formulations. Moreover, a statistical comparison between the results of the developed method and those of the reported reversed-phase high-performance liquid chromatography method showed no significant differences. This method can be used for the routine analysis of diacerein, rhein and emodin in quality control laboratories.

A highly sensitive, selective and accurate thin-layer chromatographic (TLC)-densitometric method has been developed and validated for the simultaneous determination of paracetamol (PAR) and chlorzoxazone (CZ) and their toxic impurities, 4-amino phenol (4AP) and 2-amino-4-chlorophenol (2ACP), respectively, which are also considered to be the hydrolytic degradation products and related substances of the studied drugs. A developing system consisting of chloroform-methanol-glacial acetic acid (9.5:0.5:0.25, by volume) was found to be sufficient for chromatographic separation among the four studied components using pre-activated silica gel 60 F254 TLC plates with ultraviolet detection at 225 nm. Calibration curves were constructed in the ranges of 0.3-3, 1-10, 0.06-3 and 0.04-3 µg/band for PAR, CZ, 4AP and 2ACP, respectively, using polynomial equations. The developed method was validated according to International Conference on Harmonization guidelines and demonstrated good accuracy and precision. Moreover, the method was successfully applied for the determination of PAR and CZ in different marketed samples and the results were statistically compared to those obtained by the reported reversed-phase high-performance liquid chromatography method using F-test and Student's-t test. The low detection and quantitation limits of the developed method make it suitable for quality control and stability studies of PAR and CZ in different pharmaceutical formulations.

Two accurate, precise and highly selective stability-indicating methods were adopted for simultaneous determination of benztropine mesylate (BNZ) in presence of its hepatotoxic and carcinogenic degradation product, benzophenone (BPH) either in pure form or in the pharmaceutical formulation without any preliminary separation steps. The first method is a thin layer chromatography (TLC)-densitometric method that depended on separation of BNZ from its degradate on TLC aluminum plates precoated with silica gel 60 F254 as the stationary phase using a developing system consisted of hexane: methylene chloride:triethylamine (5:5:0.6, by volume) and scanning the separated bands at 235 nm. Linear regression analysis data for the calibration plots of BNZ and BPH showed perfect linear relationships over the concentration range of 1.5-10 and 1-10 μg band-1, respectively. The second method is (UPLC) method, at which the mixture was separated on a reversed phase C8 analytical column (1.9 μm ps, 50 mm x 2.1 i.d.) using a mobile phase of acetonitrile: aqueous sodium dodecyl sulfate (50:50, v/v) Adjusted to pH = 3 with phosphoric acid, at a flow rate of 0.5 mL min-1. Quantification was achieved at 210 nm based on peak area and linear calibration curves over the concentration ranges of (20-200 μg mL-1) and (5-50 μg mL-1) for BNZ and BPH, respectively, were obtained. The investigated methods were successfully applied to available dosage form and method validation has been carried out. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by reported one and no significant differences were obtained regarding both accuracy and precision. [ABSTRACT FROM AUTHOR]

Two chromatographic methods have been established and validated for simultaneous determination of mixture of Dimenhydrinate (DMH) and Cinnarizine (CIN) in their pharmaceutical formulation and in presence of Cinnarizine impurity (1-(Diphenylmethyl) piperazine); CIN impurity. The first method was TLC-densitometric one, depends on separation and quantitation of DMH, CIN and CIN impurity on TLC silica gel 60 F 254 plates, using chloroform:methanol:glacial acetic acid:ammonia solution (9.5:0.5:0.1:0.1, by volume) as a developing system followed by densitometric measurement at 235 nm. Linear relationships were obtained in the range of 0.2–2, 0.4–1.6 and 0.1–1 μg/band for DMH, CIN and CIN impurity, respectively. The studied components were well resolved from each other with significantly different R f values of 0.35, 0.52 and 0.04 for DMH, CIN and CIN impurity, respectively. The second method was RP-HPLC, separation on C8 column using 0.05 M KH 2 PO 4 (pH = 3):methanol (35:65, v/v) as the mobile phase at a flow rate of 1 mL/min and DAD detection at 240 nm. Linear relationships were obtained in the ranges of 3–30, 2–20 and 1–10 μg/mL, with significantly different R t values of 3.27, 6.95 and 2.87 min for DMH, CIN and CIN impurity, respectively. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by reported HPLC method and no significant difference was obtained. [ABSTRACT FROM AUTHOR]

Two accurate, selective and precise chromatographic methods, namely thin-layer chromatography (TLC)-densitometric method and reversed phase high-performance liquid chromatography (RP-HPLC) method, were developed and validated for the simultaneous determination of tolfenamic acid (TOL) and its two major impurities, 2-chlorobenzoic acid (CBA) and 3-chloro-2-methylaniline (CMA), which are also reported to be its related substances. The developed TLC-densitometric method depended on separation and quantitation of the studied drugs on silica gel 60F254 TLC plates. Hexane:chloroform:acetone:acetic acid (75:25:20:0.1, v/v/v/v) was used as a developing system and the separated bands were UV-scanned at 240 nm. Linear relationships were obtained in the range of 10-100 μg band-1 for the drug and in the range of 0.1-1 μg band-1 for the studied impurities. The developed RP-HPLC depended on chromatographic separation of the studied drugs on a C18 column using 0.05 M KH2PO4 buffer (pH 3):acetonitrile (45:55, v/v) as a mobile phase delivered at constant flow rate of 1 mL min-1 with UV detection at 230 nm. Calibration curves for TOL and the two impurities were constructed over the concentration ranges of 10-100 μg mL-1 for TOL and 0.01-0.1 μg mL-1 for both CBA and CMA. Factors affecting the developed methods have been studied and optimized. Further, methods validation has been carried out according to International Conference on Harmonization guidelines. The proposed methods were successfully applied for determination of the studied drug in its bulk powder and in pharmaceutical formulation. The methods showed no significant difference when compared with the reported RP-HPLC one. The developed methods have advantages of being more sensitive and specific than the published methods. [ABSTRACT FROM AUTHOR]

Abstract: Spectrophotometric, spectrodensitometric and HPLC are stability indicating methods described for determination of Zaleplon in pure and dosage forms. As Zaleplon is easily degradable, the proposed techniques in this manuscript are adopted for its determination in presence of its alkaline degradation product, namely N-[4-(3-cyano-pyrazolo[1,5a]pyridin-7-yl)-phenyl]-N-ethyl-acetamide. These approaches are successfully applied to quantify Zaleplon using the information included in the absorption spectra of appropriate solutions. The second derivative (D2) spectrophotometric method, allows determination of Zaleplon without interference of its degradate at 235.2nm using 0.01N HCl as a solvent with obedience to Beer''s law over a concentration range of 1–10μgml−1 with mean percentage recovery 100.24±0.86%. The first derivative of the ratio spectra (1DD) based on the simultaneous use of (1DD) and measurement at 241.8nm using the same solvent and over the same concentration range as (D2) spectrophotometric method, with mean percentage recovery 99.9±1.07%. The spectrodensitometric analysis allows the separation and quantitation of Zaleplon from its degradate on silica gel plates using chloroform:acetone:ammonia solution (9:1:0.2 by volume) as a mobile phase. This method depends on quantitave densitometric evaluation of thin layer chromatogram of Zaleplon at 338nm over a concentration range of 0.2–1μgband−1, with mean percentage recovery 99.73±1.35. Also a reversed-phase liquid chromatographic method using 5-C8 (22cm×4.6mm i.d. 5μm particle size) column was described and validated for quantitation of Zaleplon using acetonitrile:deionised water (35:65, v/v) as a mobile phase using Paracetamol as internal standard and a flow rate of 1.5mlmin−1 with UV detection of the effluent at 232nm at ambient temperature over a concentration range of 2–20μgml−1 with mean percentage recovery 100.19±1.15%. The insignificance difference of the proposed methods results with those of the reference one proved their accuracy and precision. [Copyright &y& Elsevier]