Chen Sumeng, Liu Yu, Wang Yue, Wen Zeyu, Meng Jinyan, Yang Yuxin, Zhang Yang, Kong Mei, Chen Gang, Cao Xingyuan
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Qilu Animal Health Products Co., Ltd., Jinan, Shandong Province, China.
Vet Q. 2024 Dec;44(1):1-11. doi: 10.1080/01652176.2024.2407174. Epub 2024 Oct 10.
Multi-targeted tyrosine kinase inhibitor QLNC-3A6 Di-maleate, a structurally novel small molecule compound, has therapeutic efficacy for the treatment of canine cutaneous mast cell tumor (CMCT) caused by mutations in the c-Kit gene. Since pharmacokinetic (PK) information plays an important role in the development and application of new drugs, etc., a rapid, highly sensitive and selective UHPLC-MS/MS analytical method was developed and validated for the first time in this study for the quantitative detection of QLNC-3A6 in canine plasma. 100 µL of plasma was precipitated using 350 µL of acetonitrile, and Chromatographic separation was performed on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 µm) at a flow rate of 0.4 mL/min, the mobile phases were set to 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile (B). The calibration curve linear range was 0.5-100 ng/mL (>0.99). The intraday and interday precision values (relative standard deviation, RSD) were 2.06-13.57% and 6.90-9.14%. Intraday and interday accuracies were -10.73 to 9.54% and -3.86 to 0.70% respectively. The dilution integrity RSD value and stability RSD value were less than 3.77 and 7.45%, respectively. Subsequently, the pharmacokinetics were investigated in canine after oral administration of QLNC-3A6 Di-maleate tablets at a dose of 3 mg/kg BW using this method. The results showed that QLNC-3A6 showed fast absorption rate, rapid distribution and slow metabolic elimination in canine plasma. The results of the main PK parameters including z, , , and were 0.07 ± 0.01/h, 11.00 ± 2.57 h, 50.88 ± 31.94 ng/mL, 9.08 ± 11.57 h and 836.48 ± 230.53 ng h/mL, respectively.
多靶点酪氨酸激酶抑制剂QLNC-3A6二马来酸盐是一种结构新颖的小分子化合物，对治疗由c-Kit基因突变引起的犬皮肤肥大细胞瘤（CMCT）具有治疗效果。由于药代动力学（PK）信息在新药研发及应用等方面起着重要作用，本研究首次建立并验证了一种快速、高灵敏且具选择性的超高效液相色谱-串联质谱（UHPLC-MS/MS）分析方法，用于定量检测犬血浆中的QLNC-3A6。取100 μL血浆，加入350 μL乙腈进行沉淀，采用Phenomenex Kinetex C18柱（50×2.1 mm，2.6 μm）进行色谱分离，流速为0.4 mL/min，流动相设置为0.1%甲酸水溶液（A）和0.1%甲酸乙腈（B）。校准曲线线性范围为0.5 - 100 ng/mL（>0.99）。日内和日间精密度值（相对标准偏差，RSD）分别为2.06 - 13.57%和6.90 - 9.14%。日内和日间准确度分别为-10.73至9.54%和-3.86至0.70%。稀释完整性RSD值和稳定性RSD值分别小于3.77和7.45%。随后，采用该方法研究了犬口服3 mg/kg体重的QLNC-3A6二马来酸盐片剂后的药代动力学。结果表明，QLNC-3A6在犬血浆中吸收速率快、分布迅速且代谢消除缓慢。主要PK参数包括z、 、 、 和 的结果分别为0.07±0.01/h、11.00±2.5
