Journal
DRUG RESEARCH
Volume 67, Issue 10, Pages 564-575Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0043-109564
Keywords
Quercetin; Ultra High Performance Liquid Chromatography and mass spectrometry; method development and validation; self-nanoemulsifying drug delivery system; brain pharmacokinetic
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Background Quercetin (Qur) and its major in vivo bioactive metabolites i.e., 3'-O-methyl quercetin, 4'-O-methyl quercetin and quercetin 7-O-beta-D-glucuronide, may be used to treat cerebral ischemia however the poor aqueous solubility and less intestinal absorption of Qur results low bioavailability. Purpose To improve Qur bioavailability through preparation of nanoformulation and to develop and validate a sensitive quantification method for Qur detection in brain homogenate. Methods Qur-containing self-nanoemulsifying drug delivery system (Qur-SNEDDS) was developed to form oil-in-water nanoemulsions in situ. Ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric method (UHPLC/ESI-QTOF-MS/MS) was developed and validated for quantification whereas for optimal recovery of analyte, a liquid-liquid extraction method (LLE) was used. Results A droplet size of 94.633.17nm and zeta potential of -17.91 +/- 1.02mV for nanoemuslion, elution time for Qur and internal standard (IS) Rutin as 1.21 and 1.50min alongwith a transition at m/z 301.04/151.03 and 609.21/299.21, were observed respectively. Similarly, linear dynamic range (1.00ng/mL-2000.0ng/mL), intra and inter-assay i.e., %CV of 0.26-2.04, lower limit of detection (LOD) 0.08ng/mL as well as lower limit of quantitation (LOQ) as 0.131ng/mL were also observed. Conclusion The developed method have advantage over previous all methods i.e., less time consuming (<3.0), low consumption of solvents (flow rate 0.20mL/min.) via small size column, more accuracy and specificity as well as use of acetonitrile as compared to hazardous solvents. This certainly adds advantages for green chromatography technique and supports application of current developed method for quantification and evaluation of Qur-SNEDDS.
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