title: Rapid determination of canagliflozin in rat plasma by UHPLC-MS/MS using negative ionization mode to avoid adduct-ions formation.
abstract: Canagliflozin is the first sodium-glucose co-transporter-2 inhibitor, approved by the US Food and Drug Administration for the treatment of type 2 diabetes mellitus. In this study, a sensitive UHPLC-MS/MS assay for rapid determination of canagliflozin in rat plasma was developed and validated for the first time. Chromatographic separation of canagliflozin and zafirlukast (IS) was carried out on Acquity BEH C18 column (100×2.1 mm, i.d. 1.7 µm) using acetonitrile-water (80:20, v/v) as mobile phase at a flow rate of 0.3 mL min(-1). Canagliflozin and IS were extracted from plasma by protein precipitation method using acetonitrile. The mass spectrometric detection was performed using electrospray ionization source in negative mode to avoid canagliflozin adduct ions formation. Multiple reaction monitoring were used for quantitation of precursor to product ion at m/z 443.16 >364.96 for canagliflozin and m/z 574.11>462.07 for IS, respectively. The assay was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. The validated method was successfully applied to the characterization of oral pharmacokinetic profiles of canagliflozin in rats. The mean maximum plasma concentration of canagliflozin of 1616.79 ng mL(-1) was achieved in 1.5 h after oral administration of 20 mg kg(-1) in rats.
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. Electronic address: muziqbal@gmail.com.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: 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 Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Yousif A
authors.initials: YA
authors.lastname: Asiri
authors.affiliation: Department of Medical Laboratory Sciences, College of Applied Health Sciences, Taibah University, Madina, KSA & Andor Labs, Durham, NC, USA.
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
mesh_terms: D000097:Acetonitriles; D000284:Administration, Oral; D000818:Animals; D000068896:Canagliflozin; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005960:Glucosides / Q000097:blood / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007211:Indoles; D057230:Limit of Detection; D008297:Male; D048448:Phenylcarbamates; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013449:Sulfonamides; D053719:Tandem Mass Spectrometry / Q000379:methods; D013876:Thiophenes / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014105:Tosyl Compounds / Q000097:blood; D014867:Water
chemical_list: D000097:Acetonitriles; D005960:Glucosides; D007004:Hypoglycemic Agents; D007211:Indoles; D048448:Phenylcarbamates; D013449:Sulfonamides; D013876:Thiophenes; D014105:Tosyl Compounds; D014867:Water; D000068896:Canagliflozin; C062735:zafirlukast; C032159:acetonitrile
keywords: Adduct ions; Canagliflozin; Pharmacokinetics; Rat plasma; UHPLC–MS/MS