Pharmaceutical work using a SpinCore pulsed NMR spectrometer

    A SpinCore pulsed NMR spectrometer has recently been used for the quantitative analysis of medicines (Analytical Chemistry, 2009, 81, 5574 – 5576) . The experimental method was nuclear quadrupole resonance (NQR), a technique closely related to NMR  except that the energy levels and frequencies are governed by the  interaction of the nuclear electric quadrupole moment with the electric field gradient at the nuclear site. No static magnetic field is therefore required and in principle there is no limit to the volume of sample that can be examined. NQR signals are only seen in solids but the method is non-invasive, unequivocally identifies the medicine and provides an estimate of quantity.  Unlike many other techniques, there is no need to open the container or pre-treat the sample. In the paper referred to above, NQR was used to detect ³⁵Cl NQR signals at 34.33 MHz in 250 mg tablets of the antidiabetic medicine “Diabinese;” in blind tests, the number of  tablets in a standard medicine bottle could be determined to within 1 %.

    In pharmaceutical analysis, the most important quadrupolar nucleus  is ¹⁴N, found in at least 80 % of medicines. Its NQR frequencies lie below 5 MHz and so are weak, requiring long multiple pulse trains and signal averaging to achieve an acceptable signal-to-noise ratio. The sensitivity can be significantly improved and spurious signals and radiofrequency interference eliminated by the use of modern parametric data processing, enabling portable un-shielded antenna to be used in much the same way as a metal detector. Such methods have been used to detect NQR signals in a number of medicines in current use, such as the anti-hypertensive “Furosemide” and bacteriocide “Sulfapyridine” in acquisition times of several minutes, depending on the quantity ; in both, polymorphic forms can be readily distinguished, an important factor for real applications of the method (Analytical Chemistry, 2005, 77, 3925 – 3930).

    Much of this work was performed on a standard pulsed  SpinCore spectrometer by the NQR group at King’s College London using data processing algorithms developed by Professor Andreas Jakobsson at Lund University, Sweden.

J.A.S.Smith
King’s College London