Quantitative determination and pharmacokinetics of retinamido-ester in rat plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

A highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of retinamido-ester in rat plasma was developed and validated. A simplified protein precipitation with acetonitrile was employed for the sample preparation. The separation was carried out on an Agilent TC C₁₈ column (150 mm×4.6 mm ID, 5 μm particle size) with the mobile phase consisted of methanol-water-formic acid (93∶7∶0.1). Simvastatin was used as internal standard. The detection was performed on a trap-quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI). The range of calibration curve was 0.05-50 ng·mL^-1 and the limit of quantification was 10 pg·mL^-1. The intra- and inter-day precision values were between 95.97% and 104.43%, and RSD was between 4.63% and 10.69%, respectively. This method was applied to determine the pharmacokinetic parameters. The main pharmacokinetic parameters of retinamido-ester after oral administration via gastric gavage of 2.5, 5, 10 mg·kg^-1 were as follows, T_1/2: (11.28±7.23), (8.90±3.82), (8.01±5.65) h; AUC_0-∞: (103.41±61.46), (190.23±74.99), (421.66±229.20) ng·h·mL^-1; MRT: (6.31±0.75), (5.98±0.71), (6.18±0.97) h; CL/F: (30.10±13.67), (29.58±10.59), (31.18±17.51) L·h^-1·kg^-1; V_d/F: (414.94±159.82), (356.16±139.85), (369.28±322.72) L·kg^-1, respectively.