title: Gender-related pharmacokinetics and bioavailability of a novel anticancer chalcone, cardamonin, in rats determined by liquid chromatography tandem mass spectrometry.
abstract: A reversed phase liquid chromatography tandem mass spectrometry method was developed and validated for quantification of cardamonin, a potential anticancer chalcone, in rat serum. Curcumin was used as an internal standard. Following liquid-liquid extraction using n-hexane and ethyl acetate (60:40, v/v), the processed samples were chromatographed on a C18 column using acetonitrile and ammonium acetate buffer (0.01 M, pH 4.5) (85:15, v/v) as mobile phase at a flow rate of 0.6 mL min(-1). Mass spectrometric detection was performed in the negative electrospray ionization mode by multiple reaction monitoring (m/z 269→122 and 367→217 for cardamonin and curcumin, respectively). The method was validated in terms of selectivity, accuracy, precision, sensitivity, reproducibility, dilution integrity and stability. The linearity was established in the range of 1-200 ng mL(-1) (r≥0.999). The recovery of cardamonin from spiked serum was always >90%. The intra- and inter-day precision (%RSD) and accuracy (%bias) were well within the acceptable limits. The method was applied for single oral and intravenous dose pharmacokinetics in male and female Sprague Dawley rats. Following oral dose, cardamonin showed peak serum concentration that occurred at ∼2 h with very low bioavailability in both male (0.6%) and female (4.8%) rats. Cardamonin exhibited a significant gender influence on pharmacokinetics and bioavailability in rats.
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Shukla
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India. Electronic address: j_lal@cdri.res.in.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D047188:Chalcones / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; C436747:cardamonin
keywords: Bioavailability; Cardamonin; Liquid Chromatography; Pharmacokinetics; Tandem mass spectrometry