title: A Validated UPLC-MS-MS Assay for the Rapid Determination of Lorcaserin in Plasma and Brain Tissue Samples.
abstract: Lorcaserin is a novel, potent and highly efficacious 5-HT2C receptor agonist, recently approved by US Food and Drug Administration for the treatment of obesity. It has some abuse potential also and is listed as a Schedule IV drug in the Controlled Substances Act. Herein, a sensitive, selective and reliable UPLC-MS-MS assay was developed and validated for the quantitative analysis of lorcaserin in rat plasma and brain tissue using carbamazepine as an internal standard (IS). After the extraction of samples by protein precipitation, both lorcaserin and IS were separated on an Acquity BEH™ C18 (50 × 2.1 mm, 1.7 µm) column using a mobile phase consisting of acetonitrile-10 mM ammonium acetate-formic acid (85:15:0.1, v/v/v) at a flow rate of 0.25 mL/min. Detection and quantification were performed on a positive electrospray ionization interface in the multiple-reaction monitoring (MRM) mode. The MS-MS ion transitions were monitored at m/z 195.99 > 143.91 for lorcaserin and m/z 237.00 > 178.97 for IS, respectively. The calibration curves were linear over a concentration range of 1.08-500 ng/mL in plasma and 3.07-500 ng/mL in brain tissue homogenates, respectively. All the validation parameters results were within the acceptable range described in guidelines for bioanalytical method validation. The assay was successfully applied in a pharmacokinetic study of lorcaserin after oral administration in rats.
authors.affiliation: Obesity Centre, College of Medicine, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Amal A
authors.initials: AA
authors.lastname: Bajrai
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Essam
authors.initials: E
authors.lastname: Ezzeldin
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Rashood
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia muziqbal@gmail.com muziqbal@ksu.edu.sa.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002138:Calibration; D002220:Carbamazepine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D058826:Serotonin 5-HT2 Receptor Agonists / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists; D002220:Carbamazepine; C506658:lorcaserin