Lopinavir/Ritonavir: A Review of Analytical Methodologies for the Drug Substances, Pharmaceutical Formulations and Biological Matrices

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 di...

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Bibliographic Details
Published in:Critical reviews in analytical chemistry 2022-11, Vol.52 (8), p.1846-1862
Main Authors: Velozo, Carolina Trajano, Cabral, Lucio Mendes, Pinto, Eduardo Costa, de Sousa, Valéria Pereira
Format: Article
Language:English
Subjects:
Acetic acid
Acetonitrile
Analytical methods
Antiretroviral drugs
Antiviral drugs
Blood plasma
Buffers
Chromatography
Clinical trials
Coronaviruses
COVID-19
Degradation products
Drug development
Drugs
High performance liquid chromatography
HIV
Human immunodeficiency virus
Impurities
Liquid chromatography
Lopinavir
Mass spectrometry
Mass spectroscopy
Mathematical analysis
Pharmaceuticals
Pharmacodynamics
Pharmacokinetics
Pharmacology
Protease inhibitors
Proteinase inhibitors
Ritonavir
Scientific imaging
Spectroscopy
Stability analysis
Therapeutic drug monitoring
Viral diseases
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Summary: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.
ISSN:1040-8347
1547-6510
DOI:10.1080/10408347.2021.1920364