title: Development of qualitative and quantitative analysis methods in pharmaceutical application with new selective signal excitation methods for 13 C solid-state nuclear magnetic resonance using 1 H T1rho relaxation time.
abstract: Most pharmaceutical drug substances and excipients in formulations exist in a crystalline or amorphous form, and an understanding of their state during manufacture and storage is critically important, particularly in formulated products. Carbon 13 solid-state nuclear magnetic resonance (NMR) spectroscopy is useful for studying the chemical and physical state of pharmaceutical solids in a formulated product. We developed two new selective signal excitation methods in (13) C solid-state NMR to extract the spectrum of a target component from such a mixture. These methods were based on equalization of the proton relaxation time in a single domain via rapid intraproton spin diffusion and the difference in proton spin-lattice relaxation time in the rotating frame ((1) H T1rho) of individual components in the mixture. Introduction of simple pulse sequences to one-dimensional experiments reduced data acquisition time and increased flexibility. We then demonstrated these methods in a commercially available drug and in a mixture of two saccharides, in which the (13) C signals of the target components were selectively excited, and showed them to be applicable to the quantitative analysis of individual components in solid mixtures, such as formulated products, polymorphic mixtures, or mixtures of crystalline and amorphous phases.
authors.affiliation: Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Nasu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nemoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mimura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D000983:Antipyrine / Q000031:analogs & derivatives / Q000737:chemistry; D002110:Caffeine / Q000737:chemistry; D002247:Carbon Isotopes; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004338:Drug Combinations; D005079:Excipients / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009543:Nifedipine / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010615:Phenacetin / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011522:Protons; D011728:Pyridones / Q000737:chemistry; D012815:Signal Processing, Computer-Assisted; D013678:Technology, Pharmaceutical / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D002247:Carbon Isotopes; D004338:Drug Combinations; D005079:Excipients; D004364:Pharmaceutical Preparations; D011522:Protons; D011728:Pyridones; D047392:beta-Cyclodextrins; D000082:Acetaminophen; D002110:Caffeine; C019552:Saridon; D010615:Phenacetin; D011205:Povidone; D009543:Nifedipine; D007785:Lactose; D000983:Antipyrine; D007213:Indomethacin