Potential of Nuclear Quadrupole Resonance in Pharmaceutical Analysis

Abstract

Nuclear quadrupole resonance is a radio frequency (rf) spectroscopic technique, closely related to NMR, which can be used to detect signals from solids containing nuclei with spin quantum number >1/2. It is nondestructive, highly specific and noninvasive, requires no static magnetic field, and as such is currently used in the detection of explosives and narcotics. Recent technological advances in pulsed NQR methods have shortened detection times, eliminated spurious signals, and enhanced the sensitivity of detection of 14N frequencies, which lie in the low rf range of 0.4-6 MHz, encouraging a wider range of "real world" applications. This Perspective highlights some of the advantages of NQR, the applications in which it could be used, such as the quantification of pharmaceuticals and the identification of polymorphs. Other roles could include detection, analysis, and quality control of pharmaceuticals at all stages of manufacture. Finally, recent advances which enhance even further the sensitivity of detection will be discussed.

Towards Understanding Drugs on the Molecular Level to Design Drugs of Desired Profiles

“…A combination of experimental and theoretical techniques has certainly much to offer for the studies of drugs or potential drugs in early phases of drug research. Their capabilities in particular when applied to the known drugs, have been well documented in literature [92,99,101,104,105,148,[156][157][158][159][160][161][184][185][186][187][188][189]. Although in some fields the NMR or NQR are not competitive to IR, UV or XRD the examples of combined studies given above show that both techniques have a potential to elicit structural and physico-chemical information about a molecule of dug, target or the interaction drug-target.…”

“…While the number of drugs studied by solid state NMR is large, 14 [158]. 35 Cl NQR was successfully applied in the study of chloral hydrate (trichloroacetaldehyde monohydrate, 2,2,2-trichloro-1,1-ethanediol), one of the oldest synthetic agents of sedative and hypnotic effects [130], nonsteroidal anti-inflammatory diclofenac (2-[2-(2,6-dichlorophenyl) aminophenyl] acetic acid) [159], anti-diabetic chloropropamide (1-(4-chlorophenyl)sulfonyl-3-propyl-urea) [159], diuretic furosemide (4-chloro-2-furfurylamino-5-sulfamoyl-benzoic acid) [160]. Differentiation of the polymorphic forms of these compounds is not difficult because of a distinct shift in the 14 N-NQR or 35 Apart from typical NQR parameters, polymorphs are often readily identified (similarly as in NMR study) on the basis of changes in the NQR linewidth (1.5kHz for sulfapyridine, 10kHz for chloropropamide) or in the spin-lattice (sulfapyridine 70-fold, chloropropamide 2-fold) or spin-spin (chloropropamide 10%) relaxation times.…”

“…In addition, NMR and NQR are quantitative analytical techniques, i.e. the intensity of their respective signals is directly proportional to the number of nuclei in the sample [158,160,161]. Thus it is possible to estimate the quantitative polymorphous composition or a relative proportion of polymorphs in a sample and the result is reliable.…”

An Overview of NQR Signal Detection Algorithms

“…We also note that in pharmaceutical applications, it is sometimes important to know the amount of each polymorph [20,21]. …”

Repetitive experiments of one or two-pulse sequences in NQR of spins I=3/2: Liouville space, steady-state, Ernst angle and optimum signal

“…Since its discovery in the 1950s [3], [4], [5], [6], [7], [8] , it is widely used in condensed-matter physics, for instance for the study of phase transitions or polymorphism, and has also biophysical or pharmaceutical applications [9], [10], [11], [12], [13], [14].…”