Pharmaceuticals

Non-invasive detection of impurities, Quality Control of pharmaceuticals, monitoring degradation

ESR in pharmaceutical industry & research

ESR provides a simple and fast method to detect degradation of pharmaceutical products. The impact of sterilization process, stress testing and new reaction mechanisms on the degree of purity is monitored by MS 5000.


Application Example: By-Products of Sterilisation with γ-Rays

Why γ-radiation?

Since the pharmaceutical development and production includes more and more drug formulations with a controlled release of the effective substance, there will be a growing demand for biodegradable polymers. If these products are destined for parental use they have to be sterilized. Heat and steam cannot be applied because they certainly damage these substances, leaving only γ-radiation as an appropriate procedure. However, this method of sterilization could induce free radicals. The generation of radicals during this kind of treatment has been studied with the MiniScope.

Three different biodegradable polymer compositions (all PLGA polyester) have been investigated applying 25 kGy irradiation of γ-rays per sample.

Measurement parameters:

  • scan time = 60 s

  • sweep range = 15 mT

  • frequency ≈ 9.4 GHz (X-band)

Fig 1 ESR-spectra of a spin label (TEMPOL) before (dark green) and after (light green) y-irradiation.

1)  With a spin label (TEMPOL)

In the first preparation any radical induced by the y-radiation will neutralise the spin label and thus decrease its ESR signal by pairing electrons (Fig. 1, 25 kGy). Radiation induced radicals cause spin pairing with the spin label (TEMPOL) and thus decrease the ESR-signal (see Fig. 1)

Fig 2 ESR-spectra of a spin-trap (PBN) in polyester (PLGA) before (dark green) and after (light green) irradiation.

2) With a spin trap (PBN)

In the second one the short-lived radicals generated in the polyester will be trapped by the spin trap. Thus, the spectrum of the spin adduct (spin trap plus unpaired electron) appears (see Fig. 2)

Fig 3 ESR-spectrum of a polyester (PLGA) containing alanine after irradiation.

3) With alanine

In the third case, the ESR spectrum of alanine radical will show up (Fig. 3). This radical is long-term stable. Since all these experiments have been performed in a dry matrix, the nitroxyl radicals (Fig. 1 and Fig. 2) show the typical anisotropic ESR spectra of immobilised molecules.

References

  • Till Hauenschild, Joerg Reichenwallner, Volker Enkelmann, Dariush Hinderberger (2016): Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy. Chemistry, A European Journal 22, 12825 – 12838

  • Fabienne Payrot, Catherine Grillon, Catherine Vergely, Luc Rochette, Claire Ducrocq (2005): Pharmacokinetics of 1-nitrosomelatonin and detection by EPR using iron dithiocarbamate complex in mice. Biochemical Journal 387, 473 – 478