A rapid, simple and highly sensitive UPLC-MS/MS method for quantitation of pimavanserin in plasma and tissues: Application to pharmacokinetics and brain uptake studies in mice

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Apr 15:1143:122015. doi: 10.1016/j.jchromb.2020.122015.
Essam Ezzeldin  1 ,  Muzaffar Iqbal  2 ,  Yousif A Asiri  3 ,  Azza A Ali  4 ,  Toqa El-Nahhas  5
Affiliations
  • 1. Department of Pharmaceutical Chemistry and Drug Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; National Organization for Drug Control and Research, Cairo, Egypt. Electronic address: [email protected].
  • 2. Department of Pharmaceutical Chemistry and Drug Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  • 3. Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  • 4. Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls) Al-Azhar University, Cairo, Egypt.
  • 5. Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls) Al-Azhar University, Cairo, Egypt. Electronic address: [email protected].
PMID: 32174544 DOI: 10.1016/j.jchromb.2020.122015
Abstract

Pimavanserin is a new drug approved by the FDA for Parkinson's disease psychosis and Other neurological disorders such as Alzheimer's disease. In this study, we developed a UPLC-MS/MS method to quantify pimavanserin disposition in the brain and its pharmacokinetics in mice. Vilazodone was used as the internal standard. Pimavanserin and IS were extracted by liquid-liquid extraction using tert-butyl methyl ether and separated using an Acquity UPLC BEH™ C18 column. The mobile phase consisted of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in 20 mM ammonium acetate buffer) (A: B, 70:30 v/v) at a flow rate of 0.25 ml/min. The multiple reaction monitoring transitions were performed at m/z 428.23 → 98.15 for pimavanserin and m/z 441.70 > 155.03 for the IS. The developed method was found to be sensitive, fast, and reproducible. The linearity of the method was ˃0.99 over the range of 0.1-300 ng/mL in plasma and 0.25-300 ng/g in the brain homogenate. Precision and accuracy were within the acceptance range. The method was applied to pharmacokinetics and brain uptake studies, which showed that pimavanserin penetrates the blood-brain barrier and reaches a Cmax of 21.9 ± 6.66 ng/g in 2.0 h. We also found that pimavanserin brain to plasma ratio (Kbrain/plasma) is 0.16 ± 0.05 and it is rapidly eliminated.

Keywords
Brain; Mice; Parkinson's disease; Pharmacokinetics; Pimavanserin; UPLC-MS/MS.
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