A Simple and Highly Sensitive Liquid Chromatographic-Mass Spectrometric Method for the Determination of Itraconazole and Its Major Metabolite in Human Plasma and Its Application to a Bioequivalence Study

J Chromatogr Sci. 2025 Aug 30;63(8):bmaf035. doi: 10.1093/chromsci/bmaf035.

Abstract

Itraconazole is an oral triazole antimycotic drug. Bioequivalence studies are cornerstones for the approval of generic drug development globally. The present study describes a simple, sensitive and economical LC-MS/MS method for the determination of itraconazole and its metabolite in human plasma. Itraconazole (drug), hydroxyitraconazole (metabolite), and atorvastatin as internal standard were added to plasma samples. The standard curve of both the drug and metabolite covering the 4-320 ng/mL concentration range, was linear (R2 = 0.999). Also, a limit of quantification of 4 ng/mL of a sample size of 0.4 mL is achieved which is comparable or even better than the reported methods. The applicability of this method was proven by analyzing true samples obtained after the administration of 100 mg itraconazole of test (Noxifunge®) and reference (Sporanox®) to healthy volunteers. The 90% confidence intervals of the logarithmically transformed AUC0-72, AUC0-∞, and Cmax of the two formulations both for the drug and the metabolite are within the accepted levels proposed by FDA and EMA. Therefore, the presented method is suitable for bioavailability, pharmacokinetic, and bioequivalent studies in humans.

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods
  • Humans
  • Itraconazole* / analogs & derivatives
  • Itraconazole* / blood
  • Itraconazole* / chemistry
  • Itraconazole* / pharmacokinetics
  • Limit of Detection
  • Linear Models
  • Male
  • Reproducibility of Results
  • Tandem Mass Spectrometry* / methods
  • Therapeutic Equivalency

Substances

  • Itraconazole