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Summary. This study presents a selective high-performance liquid chromatography (HPLC) with diode array detection (DAD) method for the simultaneous estimation of diclofenac sodium and lidocaine hydrochloride in presence of four of their related substances and potential impurities, namely, 2,6-dimethylaniline (DMA), 2,6-dichloroaniline (DCA), N-phenyl-2,6-dichloroaniline (PDCA), and N-chloroacetyl-N-phenyl-2,6-dichloroaniline (CPDCA). Some of these related substances are reported as degradation products as well. Effective chromatographic separation was achieved using Waters Symmetry C18 column, (3.9 × 150 mm, 5 μm particle size) with gradient elution of the mobile phase composed of 0.05 M orthophosphoric acid and acetonitrile. The gradient elution started with 5% (by volume) acetonitrile, ramped up linearly to 65% in 5 min then kept constant till the end of the run. The mobile phase was pumped at a flow rate of 1.5 mL min −1 . The multiple wavelength detector was set at 220 nm, and quantification of both drugs was based on measuring their peak areas. The retention times for lidocaine and diclofenac were about 5.5 and 9.5 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 10-200 μg mL −1 for both drugs with correlation coefficients not less than 0.9998. The proposed method proved to be selective by resolution of the two drugs from their related substances and potential impurities. The validated HPLC method was successfully applied to the analysis of this binary mixture in the combined formulation (ampoules dosage form), and the assay results were favorably compared with a previously reported HPLC method. The proposed method made use of DAD as a tool for peak identity and purity confirmation.

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This study demonstrates three simple and inexpensive spectrophotometric mix-and-read assays for the determination of the skeletal muscle relaxant, baclofen (BAC) in pharmaceutical formulations. The proposed methods are based on the reaction of the primary amine group of BAC with various derivatizing reagents to yield different colored products. Method I depends on the reaction of BAC with vanillin in borate buffer pH 11.5 to give a yellow colored product with maximum absorbance at 401 nm. While method II describes the reaction with eosin Y in citric-phosphate buffer pH 2.2 forming an orange-red product measured at 548 nm. Method III depends on Hantzsch condensation reaction that yields a yellow product measured at 339 nm. Different experimental variables influencing development and stability of the obtained colored product are optimized. Validation of the three methods regarding linearity, ranges, precision, accuracy and limits of detection and quantification was performed. Regression analysis showed good linearity over the concentration ranges of 10–35, 5–20 and 5–25 μg/mL for methods I, II and III, respectively with correlation coefficient values not less than 0.999. Additionally, detection limits of BAC are 1.58, 0.94 and 0.79 μg/mL for methods I, II and III, respectively. Finally, the suggested procedures are successfully used for assay of BAC in its tablets. The main advantages of the proposed mix-and-read assays are being inexpensive and rapid with no requirement for laborious extraction techniques with equivalent or superior sensitivity compared to other published spectrophotometric procedures. Such advantages promote the suggested methods for the high throughput assay of BAC dosage forms, a critical component in quality control studies for pharmaceutical industries.

Objective This research describes the simultaneous quantitation of Paracetamol (PRM) and Lornoxicam (LRX) with five of their related substances and toxic impurities, including, 4-nitrophenol (NTP), 4-aminophenol (AMP), 4-chloroacetanilide (CAC), N-phenylacetamide (NPA), and 2-aminopyridine (APD) using a specific HPLC-DAD method. Methods The chromatographic separation involves the use of XTerra C18 column as the stationary phase and a mobile phase consisting of acetonitrile and 0.025 M phosphate buffer (pH 6). The separation was performed using gradient elution mode at 1.0 mL min−1 flow rate and detection at 260 nm for the determination of PRM and LRX. While for detecting PRM, LRX in presence of their toxic impurities, 270 nm was convenient. Validation of the suggested HPLC method was accomplished in regards to linearity, ranges, detection and quantitation limits, robustness, accuracy, precision and specificity. Results Excellent resolution of the mixture components was accomplished at retention times 4.2, 4.8, 7.4, 11.1, 13.5, 14.7 and 15.3 min for APD, AMP, PRM, NPA, LRX, NTP and CAC, respectively. Linearity was established for PRM and LRX within concentration ranges of 10–100 and 10–60 µg/mL, respectively. The correlation coefficients obtained were > 0.9997. The suggested method was confirmed to be a specific stability-indicating through the selective separation of PRM and LRX from their related substances, degradants and impurities. Conclusion The proposed method was successfully utilized for the sensitive and selective determination of PRM and LRX in their pharmaceutical formulation. Highlights To the best of our knowledge, this is the first impurity profiling assay method for this combination in presence of five of their toxic related substances and impurities. Taking into consideration that at least 2 of the studied impurities (AMP and APD) are actually reported degradation products for the main drugs, therefore the suggested method can be considered stability-indicating as well.