Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies
Authors
Shailesh Dadge
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Anees Syed
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Athar Husain
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Guru Valicherla
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Jiaur Gayen
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, β-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 × 4.6 mm, 3 µ) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 > 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (−4 °C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ’s bioanalysis and pharmacokinetic properties which is useful for future clinical trials.
Keywords: Cissus quadrangularis, LC-MS/MS, quercetin, pharmacokinetics, trans-resveratrol, validation
Author Biographies
Shailesh Dadge, Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Academy of Scientific and Innovative Research, Ghaziabad 201002, India
Athar Husain, Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
Methodology, Formal analysis, Data curation
Jiaur Gayen, Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India; [email protected] (S.D.D.);
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