TY - JOUR
T1 - Eco-friendly stability-indicating RP-HPTLC method for sildenafil analysis, characterization and biological evaluation of its oxidized stress degradation product
AU - Abdel-Kader, Maged S.
AU - Alam, Prawez
AU - Soliman, Gamal A.
AU - Al-Shdefat, Ramadan
AU - Afzal, Obaid
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - A feasible and cost effective reverse-phase high-performance thin layer chromatography (RP-HPTLC) based method was developed for the quantification of sildenafil (SLD) using eco-friendly EtOH:H2O (9.5:0.5 v/v) as mobile phase. SLD was subjected to stress conditions according to the International Conference on Harmonization (ICH) guidelines. The drug undergoes significant structural changes under oxidative stress condition to the N-oxide derivative. The oxidation product Sildenafil N-oxide (SDL N-oxide) designated in the European Pharmacopeia (EP) as impurity B was characterized utilizing 1D- and 2D-NMR as well as High Resolution Electrospray Ionization Mass Spectroscopy. The aphrodisiac potency of SDL N-oxide in comparison with SLD was evaluated in vivo using rats as experimental animal model. The evaluation based on the following parameters: mount, intromission and ejaculation latencies (ML, IL and EL, respectively), mounting and intromission frequencies (MF and IF, respectively), and postejaculatory interval (PEI). SLD N-oxide expressed similar aphrodisiac effect to SLD but with less potency. Molecular docking of SDL N-oxide along with the parent drug SLD, indicated a strong binding affinity and similar binding pattern within the active site of phosphodiesterase 5 (PDE5). However, the docking score of SLD N-oxide was slightly lower as compared to SLD in agreement with the biological study findings.
AB - A feasible and cost effective reverse-phase high-performance thin layer chromatography (RP-HPTLC) based method was developed for the quantification of sildenafil (SLD) using eco-friendly EtOH:H2O (9.5:0.5 v/v) as mobile phase. SLD was subjected to stress conditions according to the International Conference on Harmonization (ICH) guidelines. The drug undergoes significant structural changes under oxidative stress condition to the N-oxide derivative. The oxidation product Sildenafil N-oxide (SDL N-oxide) designated in the European Pharmacopeia (EP) as impurity B was characterized utilizing 1D- and 2D-NMR as well as High Resolution Electrospray Ionization Mass Spectroscopy. The aphrodisiac potency of SDL N-oxide in comparison with SLD was evaluated in vivo using rats as experimental animal model. The evaluation based on the following parameters: mount, intromission and ejaculation latencies (ML, IL and EL, respectively), mounting and intromission frequencies (MF and IF, respectively), and postejaculatory interval (PEI). SLD N-oxide expressed similar aphrodisiac effect to SLD but with less potency. Molecular docking of SDL N-oxide along with the parent drug SLD, indicated a strong binding affinity and similar binding pattern within the active site of phosphodiesterase 5 (PDE5). However, the docking score of SLD N-oxide was slightly lower as compared to SLD in agreement with the biological study findings.
UR - http://www.scopus.com/inward/record.url?scp=85111664950&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-94854-6
DO - 10.1038/s41598-021-94854-6
M3 - Article
C2 - 34321578
AN - SCOPUS:85111664950
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15358
ER -