title: High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.
abstract: A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers.
authors: Department of Family Practice & Community Health, Ajou University School of Medicine, Suwon, Korea.
authors: Doo-Yeoun
authors: DY
authors: Cho
authors: Soo Hyeon
authors: SH
authors: Bae
authors: Ji-Hong
authors: JH
authors: Shon
authors: Soo Kyung
authors: SK
authors: Bae
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D054796:Drug Dosage Calculations; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000097:blood; D011744:Pyrimidinones / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult; D000096926:Benzenesulfonamides
chemical_list: D011743:Pyrimidines; D011744:Pyrimidinones; D013449:Sulfonamides; C528397:N-dehydroxyethylmirodenafil; C528396:mirodenafil; C419664:udenafil; D000096926:Benzenesulfonamides