| Itraconazole, (ITRA for short) is known as a kind of broadspectrum antifungal triazole with low minimal inhibitory concentration (MIC) and good safety.It is hardly solube in water, so its pharmacological usages in clinical application are limited.Nano crystallization technology improves the solubility for insoluble pharmaceuticals and offers a solution for water-solubility problem of ITRA.This paper aims to develop an analytical detection method for ITRA nanocrystal formulations.Comparisons are made to illustrate applicability of each detection method.Moreover,an analytical method in blood plasma sample is also established by high-performance liquid chromatograph (HPLC for short).The concentration of ITRA in blood plasma is determined by HPLC,using pyrene as inter-standard,on a Phenomenex C18 column(5μm,250 mm×4.60 mm,Gemini), with a mobile phase consisting of 0.1% triethylamine solution(using 50% phosphase to adjust its pH to 2.5)-acetonitrile(37:63,v/v),at a flow velocity of 1.0 mL/min,with detection wavelength at EX261nm,EM365nm.Then, the method validation of the liquid phase is also examined.It is proved that the method has a good specificity.The linear range of the standard curve is from 50 to 1400 ng·mL-1 and a linear relationship is also obtained.The detection limit is 10 ng·mL-1. The coefficient of variation (CV) of inter-day and intra-day samples of high, medium and low concentration are less than 2% respectively.Meanwhile, the absolute recoveries are between 87.41%88.99%.It is indicated that this method is accurate,sensitive and can satisfy the requirements for sample analysis.The detection of ITRA plasma samples by HPLC is applied to the analysis of the blood drug concentration after intragastric infusion to rats.Moreover,the plasma concentration- time curve is plotted and different pharmacokinetic parameters are measured.Under fasting condition,AUC0-t and Cmax of ITRA nanocrystal formulations are 21129.13±1745.025 ng·mL-1·h and 844.68±86.69 ng·mL-1 respectively,while AUC0-t and Cmax of Sipirenuo capsule contents are 11409.05±4817.355 ng·mL-1·h and 460.08±89.87 ng·mL-1 respectively.Under non-fasting condition,AUC0-t and Cmax of ITRA nanocrystal formulations are 24369.14±6942.07 ng·mL-1·h and 632.92±46.84 ng·mL-1 respectively,while AUC0-t and Cmax of Sipirenuo capsule contents are 14771.32±1465.97 ng·mL-1·h and 611.67±37.12 ng·mL-1 respectively.The comparisons of the pharmacokinetic parameters conclude that AUC0-t and Cmax of ITRA nanocrystal formulations, both under fasting condition and non-fasting condition, are higher than those of Sipirenuo capsule contents.The bioavailability has been markedly improved.
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