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LC-MS/MS assay and microsomal half-life of pemigatinib

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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

Attwa MW, Abdelhameed AS, Alsaif NA, et al. · RSC advances · 2022

doi.org/10.1039/d2ra02885aRead the full paper ↗31 citationscc by

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

Structured fields used in claim comparison tables when every cited study has a complete layer.

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

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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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