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Panse, Nimishraj ; Halquist, Matthew ; Gerk, Phillip M. AAPS PharmSciTech,2023,24(7):184. DOI: 10.1208/s12249-023-02633-5 PubMed ID: 37700072
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Abstract: Ketone ester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) has gained popularity as an exogenous means to achieve ketosis. Regarding its potential as a therapeutic prodrug, it will be necessary to study its pharmacokinetic profile and its proximal metabolites (beta-hydroxybutyrate, 1,3-butanediol and acetoacetate) in humans. Here we develop and validate two LC-MS methods for quantifying KE and its metabolites in human plasma. The first assay uses a C18 column to quantitate ketone ester, beta-hydroxybutyrate and 1,3-butanediol, and the second assay uses a hydrophilic interaction liquid chromatog. (HILIC) column for the quantitation of acetoacetate. The method was partially validated for intra- and inter-day accuracy and precision based on the ICH M10 guidelines. For both the assays, the intra- and inter-run accuracy was ±15% of the nominal concentration and the precision (%CV) was <15% for all 4 mols. being quantified. The matrix effect for all mols. was evaluated and ranged from -62.1 to 44.4% (combined for all mols.), while the extraction recovery ranged from 65.1 to 119% (combined for all mols.). Furthermore, the metabolism of ketone ester in human plasma and human serum albumin was studied using the method. Non-saturable metabolism of ketone ester was seen in human plasma at concentrations as high as 5 mM and human serum albumin contributed to the metabolism of ketone ester. Together, these assays can be used to track the entire kinetics of ketone ester and its proximal metabolites. The reverse-phase method was used to study the metabolic profile of KE in human plasma and the plasma protein binding of 1,3-BD.
Keywords: bioanalysis ; human plasma ; ketone bodies ; ketone ester ; LC-MS
Purchased from AmBeed: 326-91-0
CAS No. : | 326-91-0 | MDL No. : | |
Formula : | C8H5F3O2S | Boiling Point : | - |
Linear Structure Formula : | F3CC(O)CH2C(O)(C4H3S) | InChI Key : | TXBBUSUXYMIVOS-UHFFFAOYSA-N |
M.W : | 222.18 | Pubchem ID : | 5601 |
Synonyms : |
HTTA;TTA;Thenoyltrifluoroacetone;NSC 405706;NSC 405705;NSC 405704;NSC 405703;NSC 405702;NSC 66544;TTFA
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.