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Development and Validation of an LC-MS/MS Method for the Quantitation of JNJ-64619178 (JNJ) in Mouse Plasma:

Nusrat Ahmed1, Pratiksha Kshirsagar1, Ling Ding1

  • 1Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Molecules (Basel, Switzerland)
|May 13, 2026
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) inhibition is key for treating MYC-driven medulloblastoma. A PRMT5 inhibitor, JNJ, was analyzed using a validated LC-MS/MS method, showing its pharmacokinetic profile in preclinical studies.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Protein arginine methyltransferase 5 (PRMT5) overexpression drives MYC-driven medulloblastoma.
  • PRMT5 is a potential therapeutic target for medulloblastoma.
  • JNJ is a PRMT5 inhibitor investigated in clinical trials for other cancers.

Purpose of the Study:

  • To develop and validate a bioanalytical method for quantifying JNJ in plasma and tissue.
  • To characterize the pharmacokinetic properties of JNJ in preclinical models.
  • To support in vitro and in vivo studies of JNJ in medulloblastoma.

Main Methods:

  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for bioanalysis.
  • Assay validation for sensitivity, selectivity, linearity, precision, and accuracy.
  • Pharmacokinetic studies including protein binding, Caco-2 permeability, hepatic clearance, and oral dosing in mice.

Main Results:

  • A validated LC-MS/MS method quantified JNJ in plasma and tissue with high linearity (r² = 0.99) and accuracy (91-108%).
  • JNJ exhibited >94% plasma protein binding, moderate Caco-2 permeability, and higher hepatic clearance in mice than humans.
  • Oral administration in mice resulted in low bioavailability (15%) and a Tmax of 30 min.

Conclusions:

  • A robust bioanalytical method for JNJ was established, suitable for preclinical research.
  • JNJ demonstrates specific pharmacokinetic characteristics that warrant further investigation for medulloblastoma treatment.
  • The validated method will guide future dosing strategies in medulloblastoma animal models.
Keywords:
LC-MS/MS bioanalysismedulloblastomapharmacokineticsvalidation

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