Targeted inhibition of epidermal growth factor receptor has become an important means of chemotherapy for nonsmall cell lung cancer, breast cancer, pancreatic cancer, colon cancer and other malignant tumors. Although remarkable curative effects have been achieved in the past few decades, the emergence of drug resistance is a problem. Therefore, new inhibitors need to be developed. XHL‐31 is a new candidate with significant inhibitory activity against T790M and C797S mutations in vitro. In order to study the pharmacokinetics in vivo, a sensitive and efficient UHPLC–MS/MS method was developed for the determination of XHL‐31 in rat plasma in this study. The lower limit of quantitation of this method was 1 ng/ml and the linear range was 1–2,000 ng/ml. Method validation showed a high accuracy and precision, a high stability, a high recovery and repeatability. The method was successfully applied to the pharmacokinetic study of XHL‐31 in rats. The results indicated that there were significant gender differences in oral absorption and the absolute bioavailability of XHL‐31 in female rats were extremely low (<10%).

中文翻译：

---

开发一种灵敏的UHPLC-MS / MS方法用于新型酪氨酸激酶抑制剂1- [4-（4- {5- {5--氯-4--2-（丙烷-2-磺酰基）-苯氨基]苯基]]的药代动力学研究大鼠嘧啶-2-基氨基}-苯基）-哌嗪-1-基]-丙酮

靶向抑制表皮生长因子受体已成为非小细胞肺癌，乳腺癌，胰腺癌，结肠癌和其他恶性肿瘤化疗的重要手段。尽管在过去的几十年中已经取得了显着的疗效，但耐药性的出现仍然是一个问题。因此，需要开发新的抑制剂。XHL‐31是一种新的候选药物，在体外对T790M和C797S突变具有显着的抑制活性。为了研究体内药代动力学，本研究开发了一种灵敏而高效的UHPLC-MS / MS方法测定大鼠血浆中的XHL-31。该方法的定量下限为1 ng / ml，线性范围为1–2,000 ng / ml。方法验证显示出高精度和高精度，高稳定性，高回收率和可重复性。该方法已成功应用于XHL-31在大鼠中的药代动力学研究。结果表明，雌性大鼠的口服吸收存在明显的性别差异，XHL-31的绝对生物利用度极低（<10％）。