A simple and selective UHPLC–MS/MS method for quantification of plantagoguanidinic acid in rat plasma and its application to a pharmacokinetic study

Abstract

A simple, sensitive and specific UHPLC-MS/MS method for quantification of plantagoguanidinic acid (PGA) in rat plasma was applied to investigate the pharmacokinetic behavior in vivo, using protopine as internal standard. The chromatography was separated on a Phenomenex® Luna-C column (2.1 × 150 mm, 3.0 μm) within 7.0 min using a mobile phase consisting of acetonitrile-0.1% formic acid solution under gradient elution at a flow rate of 0.4 mL/min. Prepared samples were monitored by multiple reaction monitoring mode, with the target fragmentions m/z 226.2 → 84.2 for PGA and m/z 354.2 → 188.9 for IS in positive electrospray ionization. The calibration curve of PGA was linear throughout the range 1-1000 ng/mL (r = 0.9962). The lower limit of quantitation in plasma for PGA was 0.1 ng/mL, and the recovery was >88.6%. Intra- and interday accuracy ranged from -8.6 to 4.9%. Furthermore, this validated method was successfully used for a pre-clinical pharmacokinetic study of PGA at a single dose of 20 and 5 mg/kg in rats via oral and intravenous administration. The study showed that PGA was absorpted rapidly and eliminated gradually with a greater absolute oral bioavailability of 70.1% in rats.

Drug-interaction between paclitaxel and goshajinkigan extract and its constituents

“…(n = 6 in control, n = 3 in each chemical). ***p < 0.001 vs control group evaluated by Dunnet's t-test absorbed in the unchanged form in rats orally treated with Plantago seed extract [27,28]. Paeoniflorin and catalpol are the marker compounds of Moutan bark and Rehmannia root, respectively, and these compounds are detected in the blood of rats orally treated with shimotsuto extract [29].…”

“…Next, we evaluated the inhibitory and the inducing effects of the representative constituents of GJG that can be appeared in the blood circulation after the oral administration of GJG on paclitaxel metabolism. Geniposidic acid and plantagoguanidinic acid are the marker compounds of Plantago seed [ 25 , 26 ], and these compounds can be absorbed in the unchanged form in rats orally treated with Plantago seed extract [ 27 , 28 ]. Paeoniflorin and catalpol are the marker compounds of Moutan bark and Rehmannia root, respectively, and these compounds are detected in the blood of rats orally treated with shimotsuto extract [ 29 ].…”