A modified LC-MS/MS method for determination of tetramethylpyrazine in microdialysis samples and calibration of home-made linear probes

Biomed Chromatogr. 2012 Oct;26(10):1276-81. doi: 10.1002/bmc.2689. Epub 2012 Feb 15.

Abstract

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used for the treatment of cardiovascular diseases. Several factors may affect TMP exposure after topical administration, resulting in large variability and demanding further elucidation of drug distribution. This paper describes a new efficient reliable LC-MS/MS assay for the determination of TMP in dermal microdialysate, where TMP was separated on an Agilent C(18) column (3.5 µm, 100 mm × 2.1 mm i.d.) using a mixture of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow-rate of 0.3 mL/min. The retention time was 1.89 min for TMP and 1.17 min for the internal standard (caffeine). Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for TMP was not altered through the implant lifetime. The validation and sample analysis results showed that the method is precise, accurate and well suited to support dermal microdialysis experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / surgery
  • Analysis of Variance
  • Animals
  • Calibration
  • Chromatography, Liquid / methods*
  • Drug Stability
  • Electrodes, Implanted
  • Equipment Design
  • Linear Models
  • Male
  • Microdialysis / instrumentation*
  • Microdialysis / methods
  • Pyrazines / analysis*
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Subcutaneous Tissue / surgery
  • Tandem Mass Spectrometry / methods*

Substances

  • Pyrazines
  • tetramethylpyrazine