Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.

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This paper introduces the first electrochemical approach for the determination of Fexofenadine hydrochloride and Montelukast sodium as a combined form by constructing three new graphite electrodes coated with a polymeric membrane. The first electrode was constructed using ammonium molybdate reagent as an ion pair with fexofenadine cation for the determination of Fexofenadine drug, the second electrode was constructed using cobalt nitrate as an ion pair with montelukast anion for the determination of Montelukast drug, the third electrode was prepared by incorporating the two previously mentioned ion pairs in the same graphite sensor, which makes this sensor sensitive to each Fexofenadine and Montelukast drug. The coating material was a polymeric film comprises of Poly Vinyl Chloride (PVC), Di-butyl phthalate as a plasticizer (DBP), ion pairs of drugs with previously mentioned reagents. The electrodes showed a Nernstian response with a mean calibration graph slopes of [59.227, 28.430, (59.048, 28,643)] mv.decade−1 for the three pencil electrodes respectively, with detection limits 0.025 μM for Fexofenadine and 0.019 μM for Montelukast drug which makes this method outperforms the reported method for the determination of this combination. The electrodes work effectively over pH range (2–4.5) for Fexofenadine hydrochloride and (5–9.5) for Montelukast sodium. The influence of the proposed interfering species was negligible as shown by selectivity coefficient values. The effectiveness of the electrodes continued in a period of time (45–69) days. The suggested sensors demonstrated useful analytical features for the determination of both drugs in bulk powder, in laboratory prepared mixtures and their combined dosage form. We have validated the method following ICH protocol, and we have reached very significant results in terms of the linearity, accuracy, selectivity, and precision of the method.

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A novel, simple and specific spectrofluorimetric method was developed and validated for the determination of perindopril erbumine (PDE). The method is based on the fluorescence quenching of Rhodamine B upon adding perindopril erbumine. The quenched fluorescence was monitored at 578 nm after excitation at 500 nm. The optimization of the reaction conditions such as the solvent, reagent concentration, and reaction time were investigated. Under the optimum conditions, the fluorescence quenching was linear over a concentration range of 1.0-6.0 μg/mL. The proposed method was fully validated and successfully applied to the analysis of perindopril erbumine in pure form and tablets. Statistical comparison of the results obtained by the developed and reference methods revealed no significant differences between the methods compared in terms of accuracy and precision. The method was shown to be highly specific in the presence of indapamide, a diuretic that is commonly combined with perindopril erbumine. The mechanism of rhodamine B quenching was also discussed.

Background Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties. Caffeine is one of the most common adjuvant analgesic drugs which is combined with ibuprofen in commercially available formulations. Combining analgesics offers the possibility of increasing effectiveness without increasing dose and therefore risk. Prescribing ibuprofen and caffeine together is common in clinical practice. This is the first work reporting a new and validated gas chromatographic method for the simultaneous determination of ibuprofen and caffeine in bulk and pharmaceutical dosage form. The separation was performed on a TRB-17 column (30.00 m in length, 0.25-mm ID, and 0.25-μm df). Detection was carried out using a flame ionization detector (FID). Methyl paraben was used as an internal standard. The injection volume was 1 μL with 1:50 split ratio using nitrogen as a carrier gas at a flow rate of 1 mL/min. The oven temperature was programmed at 150 °C for 0.5 min, with a rise of 10 °C/min up to 250 °C. The injector temperature was 280 °C, and the detector temperature was 300 °C. The validation of the method including linearity, range, detection limit (DL), quantitation limit (QL), accuracy, precision, specificity, system suitability, and robustness was carried out utilizing International Conference on Harmonization (ICH) guidelines. Results The retention times of methyl paraben, ibuprofen, and caffeine were 1.687, 2.594, and 4.031 min, respectively. The method was linear in the range of 1000–7000 μg/mL for ibuprofen and 162.5–1137.5 μg/mL for caffeine with a correlation coefficient of 0.9999 for both drugs. The DL was found to be 131.68 μg/mL and 15.74 μg/mL for ibuprofen and caffeine, respectively, whereas QL was found to be 399.02 μg/mL for ibuprofen and 47.68 μg/mL for caffeine. The accuracy of the method was validated by mean percentage recovery, which was found to be in the acceptable range. The precision study results of the new method were less than the maximum allowable limit percentage of relative standard deviation %RSD ≤ 2.0. The specificity was evaluated by the standard edition method, and the results of the recovery data showed that excipients do not affect the accuracy of the proposed method. The results of system suitability and robustness tests were also within the acceptable limits. Conclusion The first reported method for simultaneous determination of ibuprofen and caffeine by gas chromatography in bulk and combined dosage form was carried out in this work. The developed method gave a good separation of the drugs and internal standard. The analytical performance of the method was statistically validated as per ICH guidelines, and satisfactory results were obtained. The proposed method can be easily adopted for the routine analysis of ibuprofen and caffeine.

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