Lopinavir/ritonavir is a potent coformulation of protease inhibitors used against HIV infection. Lopinavir is the main responsible for viral load suppression, whereas ritonavir is a pharmacokinetic enhancer. Both of them have recently gained relevance as candidate drugs against severe coronavirus disease (COVID-19). However, significant beneficial effects were not observed in randomized clinical trials. This review summarizes the main physical-chemical, pharmacodynamic, and pharmacokinetic properties of ritonavir and lopinavir, along with the analytical methodologies applied for biological matrices, pharmaceutical formulations, and stability studies. The work also aimed to provide a comprehensive impurity profile for the combined formulation. Several analytical methods in four different pharmacopeias and 37 articles in literature were evaluated and summarized. Chromatographic methods for these drugs frequently use C8 or C18 stationary phases with acetonitrile and phosphate buffer (with ultraviolet detection) or acetate buffer (with tandem mass spectrometry detection) as the mobile phase. Official compendia methods show disadvantages as extended total run time and complex mobile phases. HPLC tandem-mass spectrometry provided high sensitivity in methodologies applied for human plasma and serum samples, supporting the therapeutic drug monitoring in HIV patients. Ritonavir and lopinavir major degradation products arise in alkaline and acidic environments, respectively. Other non-chromatographic methods were also summarized. Establishing the impurity profile for the combined formulation is challenging due to a large number of impurities reported. Easier and faster analytical methods for impurity assessment are still needed.

Ezetimibe (EZM) is a selective inhibitor of the sterol transporter Niemann-Pick C1-Like 1 in the small intestine used as an adjunctive therapy to lower cholesterol levels in cases of hyperlipidemia. The goal of this work was to summarize the main physical-chemical, pharmacological and pharmacokinetic characteristics of EZM, as well as to describe the main analytical methodologies for the quantification of the drug. Methods described in the United States Pharmacopeia for EZM raw material and tablets were also presented. The drug has a large number of process-related impurities and degradation products and needs strict quality control of its impurities. Specific chiral methods for the evaluation of its chiral impurities are also a need for EZM. The main advantages and disadvantages of the compiled analytical methods were presented, as well as the limits of detection and quantitation. The fastest and most efficient methods were highlighted. Most methods for analyzing EZM used C₈ or C₁₈ stationary phases in gradient mode with binary mobile phases containing acetonitrile and an acidic buffer solution with ultraviolet detection. For analysis of EZM in biological matrices, liquid chromatography-tandem mass spectrometry is generally employed using electron spray ionization in negative ionization mode using multiple reaction monitoring. Different methods in the literature evaluate a large number of impurities for EZM, however new stability-indicating high-performance liquid chromatography methods for the drug are still needed.

An important step during the development of high-performance liquid chromatography (HPLC) methods for quantitative analysis of drugs is choosing the appropriate detector. High sensitivity, reproducibility, stability, wide linear range, compatibility with gradient elution, non-destructive detection of the analyte and response unaffected by changes in the temperature/flow are some of the ideal characteristics of a universal HPLC detector. Topiramate is an anticonvulsant drug mainly used for the treatment of different types of seizures and prophylactic treatment of migraine. Different analytical approaches to quantify topiramate by HPLC have been described because of the lack of chromophoric moieties on its structure, such as derivatization with fluorescent moieties and UV-absorbing moieties, conductivity detection, evaporative light scattering detection, refractive index detection, chemiluminescent nitrogen detection and MS detection. Some methods for the determination of topiramate by capillary electrophoresis and gas chromatography have also been published. This systematic review provides a description of the main analytical methods presented in the literature to analyze topiramate in the drug substance and in pharmaceutical formulations. Each of these methods is briefly discussed, especially considering the detector used with HPLC. In addition, this article presents a review of the data available regarding topiramate stability, degradation products and impurities.