| Objective:Establish a high-performance liquid chromatography（HPLC）method to determine the blood concentration of voriconazole in human serum,collect the blood concentration results of voriconazole TDM in a third-class hospital tumor patients and the corresponding clinical data,and analyze the effect of voriconazole blood concentration in tumor patients Factors,the relationship between blood drug concentration and efficacy and safety has been preliminarily clarified.Through the analysis of the cases of voriconazole TDM in tumor patients,the importance of TDM to tumor patients and their individualized treatment experience were discussed.Methods:1.Establish an HPLC method to determine the plasma concentration of voriconazole,the chromatographic column is Eclipse Plus C18,The mobile phase is methanol:water（60:40）,the flow rate is 1 ml/min,the column temperature is 30°C,the detection wavelength is 255 nm,and the injection volume is10μL;plasma samples are processed by acetonitrile protein precipitation and separation,and sample analysis time for 10 min.2.Apply the voriconazole blood concentration monitoring method,and collect the basic data,laboratory examinations,medication status and treatment of voriconazole blood concentration monitoring in the whole hospital from January 2020 to December2020 in accordance with the inclusion and exclusion criteria process.Use SPSS 23.0statistical software to retrospectively analyze the collected data,and use Graph Pad 8.0to draw relevant pictures.3.Three typical cases of monitoring the blood concentration of voriconazole in tumor patients were analyzed,and the individualized treatment of voriconazole in tumor patients was guided.Results:1.Established an analytical method for monitoring the blood concentration of voriconazole.This method has high specificity.After plasma samples are processed,their endogenous components will not interfere with the determination of voriconazole,and the peak time is about 10 minutes.The minimum detection concentration is 0.21μg·m L-1,the regression equation is:Y=3.9726X-0.7285（R2=0.9988）,and the linear range is 0.21μg·m L-1-16.88μg·m L-1.The RSD of intraday precision is between 0.33%and 2.62%,the RSD of intraday precision is between 2.05%and 6.47%,the relative recovery rate is between 99.22%and 101.07%,and the absolute recovery rate is between 102.05%and 111.50%.The RSD of the stability of the plasma samples under the condition of 4 hours at room temperature,-20℃and 3 times of repeated freezing and thawing and 7 days at-20℃were all less than 7%.2.A total of 99 cancer patients,45 male patients and 54 female patients were included in this study.The t-test of the monitoring results of 99 tumor patients showed that the blood drug concentration of male patients was generally higher than that of female patients（P<0.05）;AST and voriconazole blood concentration of liver function indexes were significantly correlated（P<0.05）,and neutrophils The number of monocytes and the number of monocytes are significantly correlated with the plasma concentration of voriconazole（P<0.05）;there is no correlation between the results of different administration methods and the results of plasma concentration of voriconazole;the results of plasma concentration are correlated with age,weight,and time of administration by Spearman.All showed no significant correlation（P>0.05）.The plasma concentration of patients with voriconazole combined with PPIs is generally higher than that without the combination（P<0.01）.The Kruskal-Wallis test of independent samples and multiple comparison analysis showed that when voriconazole combined with carbapenems and peptide antibacterials were treated,The blood drug concentration level is higher.The incidence of adverse reactions in each concentration range was tested with the SPSS cross-scale trend chi-square test.The results showed that the incidence of adverse reactions when the blood concentration of voriconazole was≥5.5μg·m L-1was higher than that of the blood concentration within the normal range.The incidence of reaction is high,and the effective rate of treatment for those with blood drug concentration in the range of 1-5.5μg·m L-1is higher than that for those with blood drug concentration<1μg·m L-1（P<0.05）,and the difference is statistically significant.3.In the course of the research,it was found that the blood concentration of a case was as high as 8.42μg·m L-1,and the dose was adjusted by TDM to reduce the blood concentration of voriconazole to 5.42μg·m L-1,so as to achieve a good therapeutic effect;a case of voriconazole was found through TDM The interaction with omeprazole made the blood drug of voriconazole 7.54μg·m L-1.Omeprazole was discontinued to continue antifungal therapy,and the blood concentration was maintained at 3.21μg·m L-1,achieving a good effect;a case of voriconazole was found In patients with abnormal mental behavior caused by a blood concentration of 7.10·μg·m L-1,the dosage of TDM was reduced,and the blood concentration was reduced to 3.71μg·m L-1to ensure that the medication was safe and effective.Conclusion:1.The established HPLC method for the determination of voriconazole plasma concentration is highly specific,simple,accurate and sensitive,and can be used for clinical analysis of voriconazole serum samples.2.The blood concentration of voriconazole varies greatly among patients with tumors,and there are many influencing factors,and the blood concentration is significantly related to the effectiveness and safety of the treatment,and the blood concentration monitoring needs to be actively carried out.3.The analysis of actual typical cases shows that dynamic monitoring of blood drug concentration and timely adjustment of dosage according to TDM results can avoid drug interactions and reduce the occurrence of adverse reactions.It is of great significance for the rational application of voriconazole in cancer patients.Provide a basis for clinical pharmacists to formulate individualized dosing regimens for patients. |
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