LC-ESI-MS/MS analysis and pharmacokinetics of 6'-hydroxy justicidin A, a potential antitumor active component isolated from Justicia procumbens, in rats.
A sensitive and accurate LC-ESI-MS/MS method was developed and validated of for the determination of 6'-hydroxy justicidin A (HJA), a potential antitumor active component isolated from Justicia procumbens in rat plasma using a simple liquid-liquid extraction (LLE) method for sample preparation. Chromatographic separation was achieved on an Agilent Zorbax-C(18) column (2.1 mm × 50 mm, 3.5 μm) using a step gradient program with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile with 0.1% formic acid. HJA and IS (buspirone) were detected using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. This method demonstrated good linearity and did not show any endogenous interference with the active compound and IS peaks. The lower limit of quantification (LLOQ) of HJA was 0.50 ng/ml in 50 μl rat plasma. The developed and validated method has been successfully applied to the quantification and pharmacokinetic study of HJA in rats after intravenous and oral administration of 0.25 mg/kg HJA. The oral bioavailability (F) of HJA was estimated to be 36.0±13.4% with an elimination half-life (t(1/2)) value of 1.04±0.20 h.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Feng
F
Qiu
Shujun
S
Zhou
Shujun
S
Fu
Weijun
W
Kong
Shihai
S
Yang
Meihua
M
Yang
D027901:Acanthaceae / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D005561:Formates / Q000737:chemistry; D006207:Half-Life; D007275:Injections, Intravenous; D017705:Lignans / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D008297:Male; D008657:Metabolic Clearance Rate; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic; D005561:Formates; D017705:Lignans; C030544:formic acid; C571611:6'-hydroxyjusticidin A; C032159:acetonitrile