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 The treatment methods for blood blister-like aneurysm remain controversial due to its special patholog-ical structure,the risk of post-operative rebleeding and the high rate of recurrence. The arm of this paper is to access the feasibility and effectiveness of overlapping stent-assisted coiling in the treatment of blood blister-like aneurysms of the internal carotid artery. Methods Form January 2014 to December 2016,we treated 15 patients with blood blister-like aneurysm of the internal carotid artery by stent-assisted coiling in the Department of Neurosurgery,5 with two Enterprise tents,3 with three Enterprise tents,4 with Enter-prise+LVIS tents,and 3 with two LVIS tents. We determined the rate of immediate embolization of aneurysms by Raymond-Roy Occlu-sion Classification(RROC)and analyzed the clinical characteristics,postoperative complications,and follow-up data. Results All the coils and stents were successfully implanted. RROC showed 9 cases of gradeⅠ(60%),4 cases of gradeⅡ(27%),and 2 cases of gradeⅢimmediate occlusion(13%),with the parent arteries unobstructed in all the cases. Thrombosis in the stent was found in 2 cases intraoperatively,slight stent migration in 1 case,and internal carotid artery dissection in the petrous segment in another,but no cer-ebral vasospasm or aneurysm rupture in any case.Delayed cerebral in-farct was observed in 2 cases postoperatively. The patients were fol-lowed up for 2 weeks to 28 months,which showed that 11 of them were cured,2 remained stable and 2 developed further thrombosis,with an MRS score of 0-2 in 12 cases,4 in 1 case,5 in 1 case, and 6 in 1case. Conclusion Overlapping stent-assisted coiling is effective for the treatment of blood blister-like aneurysm by reduc-ing the risks of rebleeding and recurrence.