Simultaneous Determination of Thalidomide and Dexamethasone in Rat Plasma by Validated HPLC and HPTLC With Pharmacokinetic Study.

Two validated chromatographic methods have been developed for the simultaneous determination of thalidomide (THD) and dexamethasone (DEX) in rat plasma using paracetamol (PAR) as an internal standard (IS). Chromatographic analysis was achieved firstly by HPLC method on C18 column (150 × 4.6 mm2 i.d., 5 µm) and a mobile phase composed of ethanol:water (containing 0.1% acetic acid) (70:30, v/v) at the flow rate of 0.6 mL min-1. The second method was HPTLC method which depended on using a developing system of methylene chloride:acetone:ethyl acetate (7:4:1, by volume). In both methods, PAR was used as an IS. The developed methods have been validated as per FDA guidelines. All parameters were tested using quality control samples (LQC, MQC and HQC). All the obtained parameters were within the acceptance criteria. In the same way, the two methods were successfully used to study the pharmacokinetic parameters of both THD and DEX after their intra-peritoneal administration. Moreover, results obtained after administration of each drug alone were compared to those obtained after their administration together. The drugs showed drug-drug interactions when administered in combination, meaning that monitoring of such combination is very important.

Quantitative Determination of Synthesized Genotoxic Impurities in Nifuroxazide Capsules by Validated Chromatographic Methods.

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.

Validated chromatographic methods for simultaneous determination of tolfenamic acid and its major impurities.

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.