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Development and validation of a LC-MS/MS method for the pharmacokinetic study of thiamet-G and its analogues in rat

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Thesis type
(Thesis) M.Sc.
Date created
Thiamet-G inhibits the activity of N-acetyl-β-glucosaminidase, a glycoside hydrolase known as OGA. A validated bioanalytical method has been developed to enable pharmacokinetic studies of Thiamet-G and its related analogues. The bioanalysis was carried out using high performance liquid chromatography (HPLC) coupled to a tandem mass spectrometer (MS/MS). In the MS/MS, multiple reaction monitoring (MRM) was used to monitor the transition of analyte parent ions to diagnostic daughter ions. The validated method utilized the Hypercarb SPE cartridge as the cleanup tool and the ZIC-HILIC column as the suitable stationary phase. The method was validated for linearity, specificity, accuracy, precision, recovery, matrix effect, stability, and sensitivity. Pharmacokinetic samples obtained from rats treated by oral gavage with Thiamet-G were subjected to analysis using the validated method. Thiamet-G was found to be absorbed with a C max of 370 ± 20 ng / mL and showed a t max of 2 h.
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Supervisor or Senior Supervisor
Thesis advisor: Vocadlo, David J.
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