Establishment and clinical application of the method for the determination of blood concentration of apatinib / 中国药房

ABSTRACT

OBJECTIVE To establish a method for determining the blood concentration of apatinib and apply it clinically. METHODS Ultra-high performance liquid chromatography （UPLC） was used for the determination of blood concentration. The chromatographic column was ACQUITY UPLC BEH C18 with the mobile phase consisted of acetonitrile-0.1% formic acid aqueous solution （gradient elution） at the flow rate of 0.2 mL/min； the column temperature was 40 ℃， and the injection volume was 5 μL. The data of 26 cancer patients taking apatinib were collected， and their blood concentrations were measured. The correlation between patient’s blood concentration and age， dosage， adverse reactions， and combination therapy were analyzed； the levels of serum kidney injury-related factors [cystatin C （CysC）， kidney injury molecule 1 （KIM-1）， interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）] were determined before and after treatment. RESULTS The linear range of apatinib was 500-2 000 ng/mL， with a precision RSD of 3.7%， stability RSD of 4.9%， and an average sample recovery rate of 96.0% （RSD was 2.1%）. The lowest blood concentration of apatinib was 103 ng/mL and the highest was 1 932 ng/mL among 26 patients. The blood concentration of apatinib in patients showed a fluctuating downward trend with age. At a dosage of 0.125 or 0.25 g， the blood concentration of patients taking apatinib was concentrated within the range of 1 000-2 000 ng/mL. Among 26 cancer patients， 13 experienced adverse reactions， and no adverse reaction was observed in those with blood concentrations ranging from 500 to ＜1 000 ng/mL. Twenty patients were simultaneously treated with other drugs，resulting in varying blood concentration. After treatment， the levels of serum CysC， KIM-1， IL-18 and TNF- α were significantly higher than before treatment （P＜0.05）. CONCLUSIONS The established UPLC method can quickly E-mail：duanxc@ahtcm.edu.cn detect the blood concentration of apatinib. When using apatinib in clinical practice， comprehensive consideration should be given to the patient’s age， drug combination， and the attention should be paid to preventing possible acute kidney damage caused by apatinib.