title: Development of LC/MS/MS assay for the determination of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one (SK3530) in human plasma: application to a clinical pharmacokinetic study.
abstract: 5-Ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one (SK3530) is a new phosphodiesterase type-5 inhibitor currently undergoing a Phase III investigation for the treatment of male erectile dysfunction. This study first describes a rapid and sensitive LC/MS/MS assay method for the quantification of SK3530 and its major metabolite, SK3541, in human plasma. The assay was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification (LLOQ), accuracy, and precision. The multiple reaction monitoring was based on the transition of m/z=532.5-->99.1 for SK3530, 488.6-->295.5 for SK3541, and 520.3-->99.1 for SK3304 (internal standard). The assay utilized a single liquid-liquid extraction and isocratic elution, and the LLOQ was 1 ng/ml using 0.2 ml human plasma. The assay was linear over a range from 1 to 1000 ng/ml for both SK3530 and SK3541, with correlation coefficients >0.9999. The mean intra- and inter-day assay accuracy ranged from 94.7 to 101.6% and 96.8 to 101.1% for SK3530 and 92.6-105.7% and 97.4-107.8% for SK3541, respectively. The mean intra- and inter-day precision was between 7.2-12.1% and 5.7-7.4% for SK3530 and 4.6-13.2% and 5.0-14.1% for SK3541, respectively. The developed assay was applied to a clinical pharmacokinetic study after oral administration of SK3530 in healthy male volunteers (dose 100 mg).
authors: College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, Republic of Korea.
authors: Beom Soo
authors: BS
authors: Shin
authors: College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, Republic of Korea.
authors: Seul Ki
authors: SK
authors: Hu
authors: College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, Republic of Korea.
authors: John
authors: J
authors: Kim
authors: Life Science R&D Center, SK Chemicals Ltd., Suwon, Kyeonggi-do, Republic of Korea.
authors: Joon Gyo
authors: JG
authors: Oh
authors: Life Science R&D Center, SK Chemicals Ltd., Suwon, Kyeonggi-do, Republic of Korea.
authors: Won-No
authors: WN
authors: Youn
authors: Life Science R&D Center, SK Chemicals Ltd., Suwon, Kyeonggi-do, Republic of Korea.
authors: Bongyong
authors: B
authors: Lee
authors: Life Science R&D Center, SK Chemicals Ltd., Suwon, Kyeonggi-do, Republic of Korea.
authors: Key An
authors: KA
authors: Um
authors: College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
authors: Dae-Kee
authors: DK
authors: Kim
authors: R&D Center, In2Gen Co., Ltd., Seoul, Republic of Korea.
authors: Ju Young
authors: JY
authors: Lee
authors: College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, Republic of Korea. Electronic address: sdyoo@skku.ac.kr.
authors: Sun Dong
authors: SD
authors: Yoo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010601:Pharmacology, Clinical / Q000379:methods*; D011744:Pyrimidinones / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013450:Sulfones / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry
chemical_list: C518762:2-(5-(4-(2-hydroxyethyl)piperazin-1-ylsulfonyl)-2-n-propoxyphenyl)-5-ethyl-7-n-propyl-3,5-dihydro-4H-pyrrolo(3,2-d)pyrimidin-4-one dihydrochloride; D011744:Pyrimidinones; D013450:Sulfones