Sterilization of Mycobacterium tuberculosis infected samples using methanol preserves anti-tuberculosis drugs for subsequent pharmacological testing studies

Tuberculosis (Edinb). 2019 Jul:117:52-55. doi: 10.1016/j.tube.2019.06.002. Epub 2019 Jun 6.

Abstract

Pharmacokinetic/pharmacodynamic studies of anti-tuberculosis agents in animal models of tuberculosis are hampered by the frequent necessity to perform sample bioanalysis outside the biosafety level-3 environment. Thus, each specimen has to undergo tedious and time-consuming sample sterilization procedures that may also affect drug stability. Here, we tested treatment of Mycobacterium tuberculosis (Mtb) infected samples with methanol to sterilize samples while preserving drug integrity for further pharmacokinetic/pharmacodynamic evaluations. Tissue samples harvested from Mtb infected mice were homogenized, incubated in methanol, and tested for sterility. Once sterility was confirmed, the samples were used to determine concentrations of the anti-tuberculosis drug spectinamide-1599 in lung homogenates using liquid chromatography coupled with mass spectrometry. The results demonstrate that methanol sterilizes tissue samples harvested from Mtb infected mice without altering the integrity of the drug in the tissue.

Keywords: Methanol; Mycobacterium-tuberculosis; PK; Pharmacokinetics; Sample sterilization.

Publication types

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

MeSH terms

  • Animals
  • Antitubercular Agents / analysis
  • Antitubercular Agents / pharmacology*
  • Colony Count, Microbial
  • Feasibility Studies
  • Female
  • Laboratory Infection / prevention & control
  • Lung / microbiology
  • Methanol / pharmacology*
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests / methods
  • Microbial Viability / drug effects
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / physiology
  • Specimen Handling / methods*
  • Spectinomycin / analogs & derivatives
  • Spectinomycin / analysis
  • Spectinomycin / pharmacology
  • Stem Cells / drug effects
  • Sterilization / methods*
  • Tuberculosis / microbiology*

Substances

  • Antitubercular Agents
  • spectinamide 1599
  • Spectinomycin
  • Methanol