title: Quantitation of crystalline material within a liquid vehicle using 1H/19F CP/MAS NMR.
abstract: A method to detect and quantify a small amount crystalline material within a liquid solution of solubilized material is described. 19F CP-MAS ssNMR was investigated as a technique to detect low levels (0.2 mg/g) of crystalline sodium (2R)-7-{3-[2-chloro-4-(2,2,2-trifluoroethoxy)phenoxy]propoxy}-2-methyl-3,4-dihydro-2H-chromane-2-carboxylate (I) within a solid mixture (with microcrystalline cellulose) and a slurry with a liquid vehicle (capric and caprylic acid triglycerides). The results demonstrate that the area of the 19F CP/MAS signal obtained in 25 min at 25 degrees C is linearly dependent (R2=0.997) on the mass of I within the ssNMR rotor. Slopes of CP-MAS peak area versus mass of I in the rotor were nearly identical for the solid mixture and slurry suspension. Signal-to-noise ratio for the low potency slurry suggest detection and quantitation of 0.1 mg of crystalline I in the rotor, corresponding to 2 mg/g of crystalline material within the slurry suspension.
authors.affiliation: Merck & Co., Inc., Pharmaceutical R&D, 126 East Lincoln Avenue, Rahway, New Jersey 07065, USA. brian_farrer@merck.com
authors.forename: Brian T
authors.initials: BT
authors.lastname: Farrer
authors.forename: Andrey
authors.initials: A
authors.lastname: Peresypkin
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenslow
mesh_terms: D001578:Benzopyrans / Q000032:analysis* / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D014677:Pharmaceutical Vehicles; D010647:Phenyl Ethers / Q000032:analysis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D001578:Benzopyrans; D014677:Pharmaceutical Vehicles; D010647:Phenyl Ethers; D014280:Triglycerides; C518684:sodium (2R)-7-(3-(2-chloro-4-(2,2,2-trifluoroethoxy)phenoxy)propoxy)-2-methyl-3,4-dihydro-2H-chromane-2-carboxylate; C022834:miglyol 812; D011092:Polyethylene Glycols; D002482:Cellulose; C109691:microcrystalline cellulose