Using sweeping-micellar electrokinetic chromatography to determine voriconazole in patient plasma.
Invasive fungal infection is a life-threatening condition; its occurrence has increased significantly over the past 20 years. We have developed a sensitive and efficient sweeping-micellar electrokinetic chromatography (sweeping-MEKC) method to quantify voriconazole, a potent triazole antifungal drug, in patient plasma. Solid phase extraction (SPE) conditions were first optimized to minimize plasma interference while maintaining a high recovery; the sweeping-MEKC conditions were then systematically optimized to obtain a high sweeping efficiency with good selectivity. Under the optimal analytical conditions, voriconazole was baseline-separated from endogenous materials within 10.5 min with a limit of detection of 0.075 microg mL(-1). The background electrolyte comprised 40 mM phosphoric acid, 110 mM sodium dodecyl sulfate, and 20% acetonitrile. In terms of method repeatability, the relative standard deviations (RSDs) of the migration time and the peak area (intra-day; n=6) were both less than 5.5%; in terms of intermediate precision, and the RSDs of the peak area and the migration time (inter-day; n=3) were both less than 6.3%. We successfully applied this developed method to the quantitative determination of plasma voriconazole levels in 16 patients; the results correlated well with those obtained through analyses using high-performance liquid chromatography. This sweeping-MEKC method is accurate and efficient and appears to be applicable to therapeutic drug monitoring and clinical research.
Lin
Shu-Chiao
SC
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Shu-Wen
SW
Chen
Jhong-Min
JM
Kuo
Ching-Hua
CH
D000935:Antifungal Agents / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008823:Micelles; D015394:Molecular Structure; D011743:Pyrimidines / Q000097:blood*; D014230:Triazoles / Q000097:blood*; D065819:Voriconazole
D000935:Antifungal Agents; D008823:Micelles; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole