Determination of a novel low-voltage-activated calcium channel blocker (HYP-10) in rat plasma by liquid chromatography-mass spectrometry.
A novel T-type calcium channel blocker, 4-amino-1-{4-[(4-chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-butan-1-one (HYP-10) has been synthesized, and the compound has shown promise as both a nociceptive and inflammatory pain reliever as well as an analgesic in a rat neuropathic pain model. A quantification method was developed for the determination of HYP-10 in rat plasma. After simple protein precipitation with methanol, HYP-10 and the internal standard, methaqualone were chromatographed on a reversed-phase column and detected by liquid chromatography/tandem mass spectrometry with electrospray ionization. The accuracy and precision of the assay were in accordance with FDA regulations for validation of bioanalytical methods. This method was applied to measure the plasma HYP-10 concentration after a single intravenous administration of the compound in rats.
College of Pharmacy, Catholic University of Daegu, Kyoungbuk 712-702, South Korea.
Keumhan
K
Noh
Seo Young
SY
Kim
Yoo Lim
YL
Kam
Hea-Young Park
HY
Choo
Hwa Jeong
HJ
Lee
Wonku
W
Kang
D000818:Animals; D002074:Butanones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002853:Chromatography, Liquid; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D009437:Neuralgia / Q000188:drug therapy; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011506:Proteins; D051381:Rats; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
C558260:4-amino-1-(4-((4-chloro-phenyl)-phenyl-methyl)-piperazin-1-yl)-butan-1-one; D002074:Butanones; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010879:Piperazines; D011506:Proteins