Discriminative Dissolution Method Using the Open-Loop Configuration of the USP IV Apparatus to Compare Dissolution Profiles of Metoprolol Tartrate Immediate-Release Tablets: Use of Kinetic Parameters.

The use of the USP IV apparatus (flow-through cell) has gained acceptance in recent years due to its versatility and ability to discriminate due to its hydrodynamic conditions. Therefore, the objective of the present study was to develop a discriminative dissolution method in the USP IV apparatus using the open-loop configuration, as well as to propose a method to compare non-cumulative dissolution profiles obtained in the open-loop configuration considering kinetic parameters and validate its predictive power through its comparison with independent and dependent methods using five commercial immediate-release tablet drugs (one reference drug and four generic drugs) of metoprolol tartrate as a model drug. The comparison of the non-accumulated dissolution profiles consisted of determining the geometric ratio of Cmax, AUC0∞, AUC0Cmax, and Tmax (kinetic parameters) of the generic/reference drugs, whereby generic drugs "C" and "D" presented the highest probability of similarity since their 90% confidence intervals were included, or they were very close to the acceptance interval (80.00-125.00%). These results were consistent with the f2, bootstrap f2, and dissolution efficiency approaches (independent models). In conclusion, the proposed comparison method can be an important tool to establish similarity in dissolution profiles and to facilitate the development/selection of new formulations and positively ensure bioequivalence in clinical studies.

Determination of zilpaterol in a residue depletion study using LC-MS/MS in cattle plasma, muscle, liver and kidney.

Zilpaterol is a ß-agonist compound which promotes fat loss and muscle gain in cattle, providing economic benefits. However, zilpaterol residues in the animal might introduce a significant risk to humans after consumption. In the present manuscript, a highly specific, sensitive method using Selected Reaction Monitoring (SRM) in positive electrospray ionization (ESI +) mode by liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS) for plasma, muscle, liver and kidney is presented. For method development, composition of the aqueous mobile phase, precipitation agent, and solid phase extraction (SPE) conditions were optimized. The method was fully validated showing a good linearity and recovery average greater than or equal to 97 % for all matrices. The method was applied to residue depletion studies in cattle after withdrawal of zilpaterol supplementation at 3, 4, 5 and 6 days showing that tissues can be consumed by humans after 4th day of zilpaterol withdrawal.

Development and Validation of a Stability-Indicating HPLC Method for the Simultaneous Determination of trans-Resveratrol and cis-Resveratrol in an Injectable Solution.

trans-Resveratrol, a phytochemical compound with antioxidant power and various therapeutic effects, such as cardioprotective, chemopreventive, and neuroprotective, among others, has disadvantages of poor solubility and limited stability, creating difficulties for the development of new strategies for its quantification. This study developed and validated an analytical stability method for trans-resveratrol by high-pressure liquid chromatography with photodiode-array detection (HPLC-PDA), which allowed its quantification in the presence of its degradation products. The quantification of trans-resveratrol occurred at a retention time of 2.6 min, with ammonium formate (10 mM, pH = 4)/acetonitrile, 70/30 v/v, as mobile phase. The validation met the ICH Q2 criteria of specificity, method linearity (2.8-4.2 µg/ml), precision and accuracy, robustness, quantification limit (0.176 µg/ml), and detection (0.058 µg/ml). As degradation products, cis-resveratrol was observed at 3.9 min, which could be resveratrone in 3.2 min and five unidentified products in 0.7, 1.0, 1.4, 1.8, and 5 min. Some solutions subjected to temperature stress of 40 and 60°C, UV light, and acidic and basic hydrolysis exhibited colour changes. An analytical method was obtained by HPLC-PDA, which allowed quantifying the stability of trans-resveratrol in a fast and specific manner in the presence of its degradation products.