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

ABSTRACT

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 x 4.6 mm ID, 5 microm 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 x mL(-1) and the limit of quantification was 10 pg x 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 x kg(-1) were as follows, T(1/2) (11.28 +/- 7.23), (8.90 +/- 3.82), (8.01 +/- 5.65) h; AUC(0-infinity) (103.41 +/- 61.46), (190.23 +/- 74.99), (421.66 +/- 229.20) ng x h x 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 x h(-1) x kg(-1); Vd/F (414.94 +/- 159.82), (356.16 +/- 139.85), (369.28 +/- 322.72) L x kg(-1), respectively.