QbD-Driven Development and Validation of Liquid Chromatography Tandem Mass Spectrometric Method for the Quantitation of Sildenafil in Human Plasma.
The present work was employing the Quality by Design approach for the development and validation of a LC-MS-MS method to support the clinical advancement in determination of sildenafil in human plasma using lorazepam as an internal standard. Sample preparation involved solid phase extraction and calibration range observed between 3 and 1,700 ng/mL. The method was systematically optimized by employing Box-Behnken design and used mobile phase flow rate, pH and composition of mobile phase as the critical factors, and assessing the design for retention time and peak area as the responses. A substantial decrease in the variability associated with the method variables was shown in optimization studies and confirmed enhanced method robustness. The present studies revealed that developed method achieves all the regulatory requirements for linearity, accuracy, precision, selectivity, sensitivity and stability for the determination of sildenafil in human plasma. There was not any significant change in the stability of the drug shown by stability studies, performed in human plasma through freeze-thaw cycles, bench-top stability, short-term stability, long-term stability and auto sampler stability. In short, this method shows satisfactory results for the analysis of sildenafil in human plasma and possesses high degree of utility in pharmacokinetic and bioequivalence studies.
Department of Pharmaceutical Chemistry, Shri Venkateswara University, Gajrola, Amroha, UP-244236, India.
M Saquib
MS
Hasnain
Department of Biotechnology, Jiwaji University, Gwalior, MP-474001, India.
Shaukat Ali
SA
Ansari
Eminent Bioscience Pvt Ltd,New Delhi, India.
Shireen
S
Rao
College of Medicine, Shaqra University, Riyadh, Saudi Arabia.
Mohammad
M
Tabish
Department of Pharmacy, SSITM, Aligarh, UP-202001, India.
Mukul
M
Singh
Faculty of Pharmacy and Health Sciences, Universiti of Kualalampur, Royal college of Medicine, Perak, 30450 Ipoh, Malaysia.
Mohammad Syafiq
MS
Abdullah
Faculty of Pharmacy and Health Sciences, Universiti of Kualalampur, Royal college of Medicine, Perak, 30450 Ipoh, Malaysia.
Mohammed Tahir
MT
Ansari
D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000068677:Sildenafil Citrate / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000068677:Sildenafil Citrate