Simultaneous quantification of sildenafil and N-desmethyl sildenafil in human plasma by UFLC coupled with ESI-MS/MS and pharmacokinetic and bioequivalence studies in Malay population.
A simple, rapid, specific and reliable UFLC coupled with ESI-MSMS assay method to simultaneously quantify sildenafil and N-desmethyl sildenafil, with loperamide as internal standard, was developed. Chromatographic separation was performed on a Thermo Scientific Accucore C18 column with an isocratic mobile phase composed of 0.1% v/v formic acid in purified water-methanol (20:80, v/v), at a flow rate of 0.3 mL/min. Sildenafil, N-desmethyl sildenafil and loperamide were detected with proton adducts at m/z 475.4 > 58.2, 461.3 > 85.2 and 477.0 > 266.1 in multiple reaction monitoring positive mode, respectively. Both analytes and internal standard were extracted by diethyl ether. The method was validated over a linear concentration range of 10-800 ng/mL for sildenafil and 10-600 ng/mL for N-desmethyl sildenafil with correlation coefficient (r(2) ) ≥0.9976 for sildenafil and (r(2) ) ≥0.9992 for N-desmethyl sildenafil. The method was precise, accurate and stable. The proposed method was applied to study the bioequivalence between a 100 mg dose of two pharmaceutical products: Viagra (original) and Edyfil (generic) products. AUC0-t , Cmax and Tmax were 2285.79 ng h/mL, 726.10 ng/mL and 0.94 h for Viagra and 2363.25 ng h/mL, 713.91 ng/mL and 0.83 hour for Edyfil. The 90% confidence interval of these parameters of this study fall within the regulatory range of 80-125%, hence they are considered as bioequivalent.
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Kai Bin
KB
Liew
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Gabriel Onn Kit
GO
Loh
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Yvonne Tze Fung
YT
Tan
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
Kok Khiang
KK
Peh
D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008296:Malaysia; D008297:Male; D000068677:Sildenafil Citrate / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
D000068677:Sildenafil Citrate
ESI-MS/MS; Malay population; N-desmethyl sildenafil; UFLC; pharmacokinetic; sildenafil