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Accurate Mass Identification of an Interfering Water Adduct and Strategies in Development and Validation of an LC-MS/MS Method for Quantification of MPI8, a Potent SARS-CoV-2 Main Protease Inhibitor, in Rat Plasma in Pharmacokinetic Studies.
Wang, Yang; Xie, Huan; Alugubelli, Yugendar R; Ma, Yuying; Xu, Shiqing; Ma, Jing; Liu, Wenshe R; Liang, Dong.
  • Wang Y; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
  • Xie H; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
  • Alugubelli YR; Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
  • Ma Y; Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
  • Xu S; Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
  • Ma J; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
  • Liu WR; Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
  • Liang D; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Pharmaceuticals (Basel) ; 15(6)2022 May 27.
Article in English | MEDLINE | ID: covidwho-1869735
ABSTRACT
MPI8, a peptidyl aldehyde, is a potent antiviral agent against coronavirus. Due to unique tri-peptide bonds and the formyl functional group, the bioassay of MPI8 in plasma was challenged by a strong interference from water MPI8. Using QTOF LC-MS/MS, we identified MPI8•H2O as the major interference form that co-existed with MPI8 in aqueous and biological media. To avoid the resolution of MPI8 and MPI8•H2O observed on reverse phase columns, we found that a Kinetex hydrophilic interaction liquid chromatography (HILIC) column provided co-elution of both MPI8 and MPI8•H2O with a good single chromatographic peak and column retention of MPI8 which is suitable for quantification. Thus, a sensitive, specific, and reproducible LC-MS/MS method for the quantification of MPI8 in rat plasma was developed and validated using a triple QUAD LC-MS/MS. The chromatographic separation was achieved on a Kinetex HILIC column with a flow rate of 0.4 mL/min under gradient elution. The calibration curves were linear (r2 > 0.99) over MPI8 concentrations from 0.5-500 ng/mL. The accuracy and precision are within acceptable guidance levels. The mean matrix effect and recovery were 139% and 73%, respectively. No significant degradation of MPI8 occurred under the experimental conditions. The method was successfully applied to a pharmacokinetic study of MPI8 after administration of MPI8 sulfonate in rats.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Ph15060676

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Ph15060676