title: Simple and sensitive liquid chromatography-tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats.
abstract: A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction. Tadalafil and acebutolol (internal standard) were extracted by liquid-liquid extraction with tert-butyl methyl ether. The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0.1 % formic acid and acetonitrile (45:55, v/v) at a flow rate of 0.3 mL/min. The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro™ API mass spectrometer. The calibration curve was linear over a concentration range of 2-2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV %) of 10.9 %. Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL). Tadalafil was found to be stable in a battery of studies, including bench top, freeze-thaw, and autosampler conditions. The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg.
authors: Division of Biopharmaceutics, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong Dongdaemun, Seoul, 130-701, South Korea.
authors: Joo Hyun
authors: JH
authors: Lee
authors: Ju-Hee
authors: JH
authors: Oh
authors: Young-Joo
authors: YJ
authors: Lee
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D002243:Carbolines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D056148:Chromatography, Reverse-Phase / Q000592:standards; D004355:Drug Stability; D005561:Formates / Q000737:chemistry; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D008297:Male; D008738:Methyl Ethers / Q000737:chemistry; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D000068581:Tadalafil; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000097:Acetonitriles; D002243:Carbolines; D005561:Formates; D008738:Methyl Ethers; D058986:Phosphodiesterase 5 Inhibitors; C030544:formic acid; C043243:methyl tert-butyl ether; D000068581:Tadalafil; C032159:acetonitrile