A sensitive liquid chromatography-tandem mass spectrometry method for monitoring the caspofungin trough plasma concentration and its association with caspofungin efficacy in intensive-care-unit patients

Abstract

Caspofungin is a common treatment for fungal infections in intensive care unit (ICU) patients, and in these patients their pharmacokinetics are highly variable. So a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for measuring C_min in 18 ICU patients, and the exposure–response characteristics of caspofungin were investigated. The calibration curve included clinically relevant caspofungin concentrations, ranging from 0.05 to 20 mg L⁻¹. The mean recovery rate ranged from 85.2% to 95.3%, while the intra- and interday precisions were <5.5% and their accuracies were within the range of 96.2–102.3%. The overall C_min was 2.13 ± 0.99 mg L⁻¹ (mean ± SD; range, 0.51–3.79 mg L⁻¹). Patients were infected by either Candida spp. (n = 13) or Aspergillus spp. (n = 5), and caspofungin therapy was effective in 66.7% (n = 12) of them. 76.9% (10/13) patients (infected by Candida spp. and C_min > 1 mg L⁻¹) achieved clinical success while 23.1% (3/13) patients (C_min > 1 mg L⁻¹: n = 1; C_min < 1 mg L⁻¹: n = 2) failed to show a clinical response. All five patients infected by Aspergillus spp. had a mean plasma C_min above 0.5 mg L⁻¹, and only two achieved clinical success. Validated LC-MS/MS is a simple, rapid and accurate method that is suitable for monitoring the concentration of caspofungin. C_min exhibits a wide range in ICU patients, and relatively good treatment results are obtainable when C_min exceeds the 90% minimal inhibitory concentration (Candida spp: 1 mg L⁻¹; Aspergillus spp: 0.5 mg L⁻¹).