title: Rapid and sensitive determination of udenafil in plasma by LC-MS/MS for intranasal pharmacokinetic study in rats.
abstract: A rapid and sensitive analytical method for udenafil in rat plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This chromatographic procedure was then applied to the in vivo pharmacokinetic studies in rats for determining the advantages of intranasal administration of the drug over oral administration. Using liquid-liquid extraction (LLE), udenafil and the internal standard (IS) sildenafil were extracted with dichloromethane from 100 μl of plasma samples. Chromatographic separation was performed using Pursuit XRS C₁₈ column (50 mm × 2.1 mm, i.d., 3 μm, Varian Inc., CA, U.S.A.) with an isocratic mobile phase consisting of acetonitrile and 10 mM ammonium acetate (90 : 10, v/v) at a flow rate of 0.2 ml/min over a total run time of 2.5 min. Detection and quantification was performed by mass spectrometry using the multiple reaction-monitoring mode at m/z 517.4→283.1 for udenafil and m/z 475.3→100.0 for IS. Results showed that the developed method was sensitive and specific for udenafil. Linearity was obtained in the range of 0.5-1000 ng/ml. The coefficient of variation of both intra- and inter-day validation were below 11.6% and the intra- and inter-day accuracy ranged from 91.5 to 109.9%. Udenafil concentration was successfully measured from plasma after intranasal as well as after intravenous or oral administration at clinical dose (1.67 mg/kg) in rats. Moreover, the T(max) values obtained from pharmacokinetic studies suggested that administration of udenafil intranasally could be more effective than by the oral route.
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University.
authors: Wan-Sung
authors: WS
authors: Ku
authors: Hyun-Jong
authors: HJ
authors: Cho
authors: In-Soo
authors: IS
authors: Yoon
authors: Jeong Hoon
authors: JH
authors: Kim
authors: Bong-Jin
authors: BJ
authors: Cha
authors: Jung Sun
authors: JS
authors: Kim
authors: Kyeong-Mi
authors: KM
authors: Kim
authors: Shin-Kwon
authors: SK
authors: Kang
authors: Suk-Jae
authors: SJ
authors: Chung
authors: Chang-Koo
authors: CK
authors: Shim
authors: Dae-Duk
authors: DD
authors: Kim
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D059625:Liquid-Liquid Extraction; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D010879:Piperazines / Q000737:chemistry / Q000302:isolation & purification / Q000592:standards; D011687:Purines / Q000737:chemistry / Q000302:isolation & purification / Q000592:standards; D011743:Pyrimidines / Q000097:blood* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000097:blood* / Q000302:isolation & purification; D013450:Sulfones / Q000737:chemistry / Q000302:isolation & purification / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D000096926:Benzenesulfonamides
chemical_list: D008752:Methylene Chloride; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D011743:Pyrimidines; D000068677:Sildenafil Citrate; D013449:Sulfonamides; D013450:Sulfones; C419664:udenafil; D000096926:Benzenesulfonamides