ABSTRACT
Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.
ABSTRACT
OBJECTIVE:To establish a method for the determination of related substances in lorcaserin hydrochloride.METHODS:HPLC method was adopted.The determination was performed on Welch ultimate XB-ODS column with mobile phase consisted of Sodium dihydrogen phosphate (pH =6.5)-acetonitrile (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 220 nm,and column temperature was 35 ℃.The sample size was 20 μL.RESULTS:The linear ranges of impurity 1,2,3 were 0.075 60-7.560 μg/mL(r=0.999 9),0.081 40-8.140 μg/mL(r=0.999 9),0.099 24-9.924 μg/mL(r=0.999 9),respectively.The limits of quantification were 0.075 60,0.081 40,0.099 25 μg/mL.The limits of detection were 0.022 68,0.024 42,0.029 77 μg/mL.RSD of precision test was lower than 2.0％.Impurity 1 was found in stability test and reproducibility test,RSD＜2.0％.The recoveries were 98.53％-102.45％ (RSD=1.06％,n=9),98.26％-101.64％ (RSD=1.03 ％,n=9),100.08％-102.10％ (RSD=0.70％,n=9),respectively.CONCLUSIONS:The method is sensitive,rapid,accurate and reliable,which can be used to determine the related substances of lorcaserin hydrochloride.