TY - JOUR
T1 - 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
T2 - application to a clinical pharmacokinetic study
AU - Shin, Beom Soo
AU - Hu, Seul Ki
AU - Kim, John
AU - Oh, Joon Gyo
AU - Youn, Won No
AU - Lee, Bongyong
AU - Um, Key An
AU - Kim, Dae Kee
AU - Lee, Ju Young
AU - Yoo, Sun Dong
PY - 2007/9/21
Y1 - 2007/9/21
N2 - 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).
AB - 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).
KW - LC/MS/MS
KW - PDE-5 inhibitor
KW - Pharmacokinetics
KW - SK3530
KW - SK3541
UR - http://www.scopus.com/inward/record.url?scp=34548486958&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2007.06.021
DO - 10.1016/j.jpba.2007.06.021
M3 - Article
C2 - 17689219
AN - SCOPUS:34548486958
SN - 0731-7085
VL - 45
SP - 176
EP - 184
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
IS - 1
ER -
