Development and validation of UPLC-MS/MS method for in vitro quantitative analysis of pyrazinamide in lipid core-shell nanoarchitectonics for improved metabolic stability
| Autor: | Subham Banerjee, Aishwarya Jala, Maharshi Thalla, Roshan M. Borkar |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Acta Chromatographica. 34:237-245 |
| ISSN: | 2083-5736 1233-2356 |
| Popis: | Pyrazinamide (PZA), a medication for tuberculosis, has high aqueous solubility and low permeability, undergoes extensive liver metabolism, and exhibits liver toxicity through its metabolites. To avoid this, PZA in lipid core-shell nanoarchitectonics has been formulated to target lymphatic uptake and provide metabolic stability to the incorporated drug. The UPLC-MS/MS method for reliable in vitro quantitative analysis of pyrazinamide (PZA) in lipid core-shell nanoarchitectonics as per ICH guidance was developed and validated using the HILIC column. The developed UPLC-MS/MS method is a simple, precise, accurate, reproducible, and sensitive method for the estimation of PZA in PZA-loaded lipid core-shell nanoarchitectonics for the in vitro determination of % entrapment efficiency, % loading of pyrazinamide, and microsomal stability of lipid core-shell nanoarchitectonics in human liver microsomes. The % entrapment efficiency was found to be 42.72% (±12.60). Lipid nanoarchitectonics was found to be stable in human liver microsomes, where %QH was found to be 6.20%, that is, low clearance. Thus, this formulation is suitable for preventing PZA-mediated extensive liver metabolism. These findings are relevant for the development of other lipid-mediated, suitable, stable nanoformulations containing PZA through various in vitro methods. |
| Databáze: | OpenAIRE |
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