title: Quantification of curcumin, demethoxycurcumin, and bisdemethoxycurcumin in rodent brain by UHPLC/ESI-Q-TOF-MS/MS after intra-nasal administration of curcuminoids loaded PNIPAM nanoparticles.
abstract: An ultra high performance liquid chromatography-electrospray ionization-synapt mass spectrometric method (UHPLC/ESI-QTOF-MS/MS) for the analysis of curcumin (Cur), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) in Wistar rat brain homogenate was developed and validated. The chromatographic separation was achieved on a Waters ACQUITY UPLC™ BEH C18 (2.1mm × 100 mm; 1.7μm) column using isocratic mobile phase, consisting of acetonitrile: 10mM ammonium formate: formic acid (90:10:0.05v/v/v), at a flow rate of 0.2 ml min(-1) . The transitions occurred at m/z 367.0694/217.0598, 337.0717/173.0910, 307.0760/187.0844 for Cur, DMC, BDMC and m/z 307.0344/229.0677 for the IS (Nimesulide) respectively. The recovery of the analytes from Wistar rat brain homogenate was optimized using liquid-liquid extraction technique (LLE) in (ethyl acetate: chloform) mixture. The total run time was 3.0 min and the elution of Cur, DMC, BDMC occurred at 1.6, 1.75, 1.70 min, and for the IS 1.87 min, respectively. The linear dynamic range was established over the concentration range of 1.00 ng mL(-1) to 1000.0 ng mL(-1) (r(2) ; 0.9909 ± 0.0011, 0.9911 ± 0.003, and 0.9919 ± 0.0013) for Cur, DMC, and BDMC, respectively. The intra and inter-assay accuracy in terms of % CV for Cur, DMC, and BDMC was in the range 0.47-2.20, 0.47-1.65, and0.44-2.70, respectively. The lower limit of detection (LOD) and quantitation (LOQ) for Cur, DMC, and BDMC were 0.46, 0.05, 0.16 ng mL(-1) and 0.153, 0.015, 0.052 ng mL(-1) , respectively. Analytes were stable and the method proved to be accurate (recovery, >85%), specific and was applied to evaluate the Cur, DMC, BDMC loaded PNIPAM NPs as vehicles for nose to brain drug delivery.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Department of Pharmaceutics, New Delhi-, 110062, India.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmad
authors.forename: Musarrat Husain
authors.initials: MH
authors.lastname: Warsi
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Mohd
authors.initials: M
authors.lastname: Samim
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000281:Administration, Intranasal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D036381:Diarylheptanoids; D057230:Limit of Detection; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D036381:Diarylheptanoids; C052970:poly-N-isopropylacrylamide; C034786:bisdemethoxycurcumin; D003474:Curcumin; C050229:demethoxycurcumin
keywords: PNIPAM nanoparticles; UHPLC-MS/MS-ESI-Q-TOF; bisdemethoxycurcumin; curcumin; demethoxycurcumin