Total drug quantification in prodrugs using an automated elemental analyzer

Drug Deliv Transl Res. 2019 Dec;9(6):1057-1066. doi: 10.1007/s13346-019-00649-8.


Polymeric prodrugs have become an increasingly popular strategy for improving the pharmacokinetic properties of active pharmaceutical ingredients (API). Therefore, identifying a robust method for quantification of the API in these prodrug products is a key part of the drug development process. Current drug quantification methods include hydrolysis followed by reversed phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC)-based molecular weight determination, and mass spectrometry. These methods tend to be time-consuming and often require challenging method development. Here, we present a comparative study highlighting the automated elemental analyzer as a facile approach to drug quantification in this up-and-coming class of therapeutics. A polymeric prodrug using poly(L-lysine succinylated) (PLS) and the drug lamivudine (LAM) was prepared and analyzed using the elemental analyzer in comparison to the traditional approaches of hydrolysis followed by RP-HPLC and SEC using multi-angle light scattering (MALS) detection. The elemental analysis approach showed excellent agreement with the conventional methods but proved much less laborious, highlighting this as a rapid and sensitive analytical method for the quantitative determination of drug loading in polymeric prodrug products.

Keywords: Drug loading; Elemental analysis; Nanomedicine; Nanoparticle; Polymer–drug conjugates; Prodrug.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Hydrolysis
  • Lamivudine / analysis*
  • Lamivudine / chemistry
  • Polylysine / analogs & derivatives*
  • Polylysine / chemistry
  • Prodrugs / analysis*
  • Prodrugs / chemistry
  • Scattering, Radiation


  • Prodrugs
  • Polylysine
  • Lamivudine