title: Analysis of bacopaside I in biomatrices using liquid chromatography-tandem mass spectrometry: Pharmacokinetics and brain distribution in Swiss-albino mice.
abstract: Bacopaside I (BP-I) is the major pseudojujubogenin glycoside of Bacopa monniera (BM) extract which has been widely used as a nerve tonic to improve the memory and intellect of human beings from ancient times. A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of BP-I in mouse plasma and brain homogenate has been developed and validated. All biosamples were processed by liquid-liquid extraction and chromatographed on C18- reversed phase column using mobile phase consisting of ammonium acetate (10mM, pH 4) - acetonitrile (10:90, v/v) at a flow rate of 0.5mL/min. The detection was performed in negative electrospray ionization mode and the precursor/product ion transitions of BP-I and internal standard (IS) hydrochlorothiazide were quantified in multiple reaction monitoring (MRM) using QTRAP-5500 MS/MS. The linearity was established over the concentration range of 0.5-2000ng/mL (r(2)>0.990), with lower limit of quantification (LLOQ) of 0.5ng/mL in both plasma and brain matrix. Within- and between-run precision and accuracy were well within the acceptable limits of variation. Consistent and reproducible recovery (>70%) was obtained with insignificant matrix effect for BP-I and IS. The method fulfilled US Food and Drug Administration (USFDA) guidelines for bioanalytical method validation in terms of selectivity, sensitivity, linearity, accuracy, precision, matrix effect, dilution integrity, carry-over effect and stability. Further, the method was successfully applied to execute the plasma pharmacokinetics and brain distribution of BP-I in Swiss-albino mice following intravenous administration at a dose of 5mg/kg.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow , 226031 Uttar Pradesh , India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Bhateria
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow , 226031 Uttar Pradesh , India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Rachumallu
authors.initials: R
authors.lastname: Ramakrishna
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow , 226031 Uttar Pradesh , India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Puttrevu
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow , 226031 Uttar Pradesh , India.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Singh
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow , 226031 Uttar Pradesh , India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: rabi_bhatta@cdri.res.in.
authors.forename: Rabi Sankar
authors.initials: RS
authors.lastname: Bhatta
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D051379:Mice; D012015:Reference Standards; D015203:Reproducibility of Results; D012503:Saponins / Q000032:analysis* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014315:Triterpenes / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D012503:Saponins; D014315:Triterpenes; C442170:bacopaside I
keywords: Bacopa monniera; Bacopaside I; Brain-to-plasma ratio; LC–MS/MS; Pharmacokinetics; Tissue distribution