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Two validated methods for the simultaneous determination of ibuprofen and famotidine in the presence of ibuprofen impurity (4-isobutylacetophenone) and/or famotidine degradation products were described. The first method was a simple TLC method where separation was performed on silica gel plates using ethyl acetate: methanol: ammonia (9:2:1, by volume) as a mobile phase. R f values were found to be 0.40, 0.94, 0.66, 0.27, 0.83 for ibuprofen, 4-isobutylacetophenone, famotidine, famotidine acid and basic degradation products, respectively. The second method was HPLC on C18 column using methanol: phosphate buffer pH 3 (80:20, v/v) as a mobile phase. Retention times were found to be 2.2 min, 9.9 min, and 8.6 min for famotidine, ibuprofen, and 4-isobutylacetophenone, respectively. Both methods were validated according to the ICH guidelines and applied for the determination of the two drugs in pure powder and combined dosage form without interference from the excipients.

Background: The utilization of selection methods such as genetic algorithm (GA) aims to construct better partial least squares (PLS) and principal component regression (PCR) models than those established from the full-spectrum range. Objective: Determination of paracetamol (PAR), orphenadrine citrate (Or.cit), and caffeine (CAF) in the presence of PAR nephrotoxic impurity [p-aminophenol (PAP)]. GA was applied to select the optimum wavelengths used. Methods: A calibration set was prepared in which the three drugs, together with PAP, were modeled by multilevel multifactor design. This calibration set was used to build the PLS and PCR models, either with or without preprocessing the data using GA. Results: Results were compared with and without preprocessing, and this revealed that GA can find an optimized combination of spectral wavelengths, yielding a lower root mean square error of prediction as well as a lower number of latent variables used. The results of the two models show that simultaneous determination of the aforementioned drugs can be performed in the concentration ranges of 20–60, 3–11, and 1–9 μg/mL for PAR, Or.cit, and CAF, respectively. Conclusions: The proposed models were applied for the determination of the three drugs in their pharmaceutical formulations, and the results were verified by the standard addition technique. Highlights: GA can be useful as a wavelength selection tool before applying multivariate PLS and PCR methods. GA gives an improvement in the predictive ability of the models with lower RMSEP and less number of latent variables (LVs). The proposed PLS, PCR, GA-PLS, and GA-PCR spectrophotometric methods were able to determine paracetamol, orphenadrine citrate, and caffeine in the presence of p-aminophenol and severe spectral overlapping.

Three chromatographic methods were developed, optimized and validated for Paracetamol (PAR), Orphenadrine citrate (Or.cit) and Caffeine (CAF) determination in their mixture and in presence of PAR toxic impurity; P-aminophenol (PAP) in tablets. The first method is based on a thin layer chromatography combined with densitometry. Separation was achieved using silica gel 60 F254 TLC plates and dichloromethane:methanol:acetone:glacial acetic acid (9:1:0.5:0.3, v/v/v) as a developing system at 230 nm. The second method is based on high-performance liquid chromatography with diode array detection. The proposed compounds are separated on a reversed phase C18 analytical column using phosphate buffer (pH 9; 0.05 M) and methanol (80:20, v/v) at 1.2 mL/min. Linear regressions are obtained in the range of 1–500 μg/mL, 25–1000 μg/mL and 1–400 μg/mL for PAR, Or.cit and CAF, respectively. Quantification of the toxic PAP is carried out using LC–MS-MS by electrospray ionization in the positive mode using triple quadrupole mass spectrometry. The limit of quantification for PAP is 1 ng/mL. All methods are validated according to the ICH guidelines and successfully applied to determine PAR, Or.cit, CAF and PAP in pure powder and in combined tablets dosage form without interference from excipients.

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