LC-MS/MS assay and microsomal half-life of pemigatinib
A two-minute LC-MS/MS method quantifies pemigatinib in human liver microsomes and finds a 27.29 min half-life and moderate CLint.
Source
A validated LC-MS/MS analytical method for the quantification of pemigatinib: metabolic stability evaluation in human liver microsomes
Study at a glance
- Design
- Other — Validated C18 MRM LC-MS/MS of pemigatinib in human liver microsomes with well-stirred clearance model
- N
- Bioanalytical method validation and in-vitro HLM kinetics — no subject N
- Population
- Human liver microsome incubations of pemigatinib
- Outcome
- Quantification performance and in-vitro t½ / CLint of pemigatinib
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Inspect source passages
LC-MS/MS assay and microsomal half-life of pemigatinib
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
In vitro t1/2 of PMB is 27.29 min.
Our findings revealed that PMB an in vitro t 1/2 values of 27.29 min and a moderate CL int (25.4 μL min −1 mg −1 ), which suggest a moderate rate of hepatic clearance.
Mean recovery of PMB is 101.7 ± 4.48%.
The mean recovery of PMB the current methodology is 101.7 ± 4.48% that is better compared to the reported method (89.3–92.2%).
What they did
Authors developed a C18 MRM method (pemigatinib 488→401/186, flavopiridol IS), validated QCs at 5–400 ng mL−1 after ACN precipitation from HLM, and used an in vitro t1/2 well-stirred model for clearance.
What they found
Mean recovery is 101.7 ± 4.48%. In vitro t1/2 is 27.29 min and CLint is 25.4 μL min−1 mg−1, implying moderate hepatic extraction rather than ultra-rapid clearance.
The limits
What it doesn't show
No patient pharmacokinetic curves; HLM t1/2 is an in vitro predictor, and the authors note in vivo TDM still needs future work.
Key terms
- Pemigatinib (PMB)
- FGFR1–3 inhibitor; analyte quantified here.
- MRM
- Multiple reaction monitoring of precursor→product ion pairs on a triple quadrupole.
- Intrinsic clearance (CLint)
- Microsomal consumption rate used to predict hepatic extraction.
- In vitro t1/2
- Half-life of parent drug in an HLM incubation.
- HLM
- Human liver microsomes containing CYPs for metabolic stability tests.
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Quiz yourself
PMB in vitro t1/2 in HLM is:
Common questions
How fast is the LC run?
2 min; PMB elutes at 1.2 min.
What t1/2 and CLint were found?
27.29 min and 25.4 μL min−1 mg−1.
Internal standard?
Flavopiridol (FLV).
Extraction?
Acetonitrile protein precipitation from HLM.
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