Comparative Bioequivalence Study of 2 Clopidogrel 75-mg Tablet Formulations in Moroccan Volunteers.

This study investigates the pharmacokinetic properties and bioequivalence of 2 formulations of clopidogrel tablets administered to a cohort of healthy Moroccan male volunteers. The primary objective was to assess the rate and extent of drug absorption from the test formulation in comparison to a reference formulation, focusing on critical parameters including maximum plasma concentration (Cmax), area under the concentration-time curve from 0 to the last measurable time (AUC0-t), and area under the concentration-time curve extrapolated to infinity (AUC0-∞). The results revealed that the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for the test formulation relative to the reference formulation were 105.7%, 105.6%, and 105.6%, respectively. The 90% confidence intervals for these parameters fell within the predefined bioequivalence range of 80%-125%, indicating a statistically and clinically equivalent performance between the 2 formulations. This investigation sheds light on the pharmacokinetic behavior of clopidogrel in the context of the Moroccan male population, offering valuable insights into the comparability of formulations.

Overview of the bioanalytical methods used for the determination of benzodiazepines in biological samples and their suitability for emergency toxicological analysis.

Benzodiazepines are one of the most widely used classes of drugs around the world. They are medically used in different therapeutic areas including insomnia, anxiety, epilepsy, and anesthesia. Unfortunately, these drugs are very widespread in the illicit market for recreational purposes and cause drug dependence, traffic accidents, and criminality. Furthermore, benzodiazepine misuse leads to acute poisoning cases that often end up in hospital emergency rooms. Therefore, it is crucial for hospitals to possess straightforward and efficient bioanalytical techniques that enable the swift detection of benzodiazepines in biological samples. This review provides a general overview of the different bioanalytical techniques used for the detection and quantification of benzodiazepines in biological samples and emphasizes their suitability for emergency toxicological analyzes.

Intra-GUM comparisons for the estimation of measurement uncertainty: Application to a chromatographic assay of four statins in a dry form.

The chromatographic method (HPLC) is well-known for its dependability and precision in pharmaceutical analyses for assessing the quality and efficacy of drug products. However, the characteristics of the HPLC method make sense only after a careful evaluation of the measurement uncertainty. Nevertheless, it has been observed that precise identification of the sources of uncertainty resulting from the operational mode using the HPLC technique to assess their standard uncertainty based on the ISO-GUM approach is not obvious. Because of our extensive bibliographic search, we noticed that many studies published on the estimate of the uncertainty in chromatographic methods (HPLC) using the Eurachem/Citac guide are somewhat diverse in their use of this approach. The documentary research revealed four mathematical models namely, GUM1, GUM2, GUM3, and GUM4 that are most used to estimate the measurement uncertainty of the HPLC technique. Hence, a comparison between the four GUM mathematical models was carried out graphically and statistically using one-way ANOVA followed by Tuckey and Scheffe tests. The comparison results show a significant difference, which may create confusion in the reporting of measurement results as well as problems in making sound decisions. This leads to the suggestion that alternative approaches, such as the approach of a total error or ISO 11325, be used to check the ISO-GUM method's calculations of measurement uncertainty.

Optimization of a Ligand Exchange Chromatography Method for the Enantioselective Separation of Levofloxacin and Its Chiral Impurity.

BACKGROUND: Levofloxacin is a third-generation fluoroquinolone that has several advantages over its (R) ofloxacin isomer. It is used to treat different types of infection, including urinary infection and prostatitis. OBJECTIVE: A new HPLC method for the enantioselective separation of levofloxacin and its chiral impurity was developed and validated to improve the separation of the enantiomers of levofloxacin [impurity(R) and active principle (S)] by increasing the value of the resolution between the eutomer and the distomer. METHOD: Chromatographic separation was performed on a Prodigy ODS -2, 5 µm 4.6 × 150 mm column, with a gradient of buffer solution and methanol (80:20, v/v). A Box-Behnken design was considered when optimizing the enantioseparation involving the effects of many factors such as the concentration of d-phenylalanine, the pH of the buffer, the percentage of organic modifier in the mobile phase, the flow rate, the temperature of the column, and the type of column. RESULTS: Chiral separation was achieved with an optimal resolution of 3.8. The method was successfully validated following the International Conference on Harmonization Q2 (R1) guideline, fulfilling the acceptance criteria for selectivity [no interference in the retention time of (S) levofloxacin and (R) levofloxacin], linearity (r ≥0.999 in the range 1.25-3.75 µg/mL for all enantiomers), and precision (RSD <2%). Accuracy was assessed by the application of the analytical method to an analyte of known purity, providing evidence for the usefulness of this monitoring system. CONCLUSIONS: The method was successfully used for the determination of levofloxacin impurity in raw material and pharmaceutical dosage forms. HIGHLIGHTS: The following method is accurate and robust to quantify and characterize the presence of levofloxacin impurity in raw material for pharmaceutical compounds.