Henry Ford Health System, Detroit, MI 48202, USA.
Anal Bioanal Chem. 2010 Mar;396(5):1741-4. doi: 10.1007/s00216-009-3385-5. Epub 2009 Dec 31.
Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged at 14,000 rpm at 4 °C for 25 min. The supernatant was injected in an HPLC system comprising a Waters Symmetry NH(2) column, a mobile phase of acetonitrile/water (95/5, v/v), a flow rate of 1.0 mL/min, at 220 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 9 ng/mL, and a good precision with a coefficient variation of 1.65, 1.86, and 1.26% for 20, 400, and 800 ng/mL, respectively. With this simple method, excellent separation and sensitivity of latrunculol A are achieved, thus allowing a rapid analysis of the plasma samples for absorption, distribution, and metabolism studies.
拉氏囊素 A 是一种最近发现的 6,7-二羟基类似物，具有强大的肌动蛋白抑制剂拉氏囊素 A 的活性。拉氏囊素 A 在体外对小鼠和人结肠肿瘤细胞系的细胞毒性比拉氏囊素 A 更强。目前，尚无关于拉氏囊素 A 在体内生物利用度的报道。本研究旨在进行药代动力学评估，这是首次研究拉氏囊素 A 的生物利用度。在本研究中，开发了一种简单的血浆制备和快速 HPLC 方法。首先用乙腈处理含有拉氏囊素 A 的小鼠血浆，然后在 4°C 下以 14,000 rpm 的速度离心 25 分钟。上清液注入 HPLC 系统，系统包括 Waters Symmetry NH(2)柱，乙腈/水（95/5，v/v）为流动相，流速为 1.0 mL/min，检测波长为 220nm。该方法通过参数进行了验证，包括良好的线性相关性、定量下限为 9ng/mL，以及良好的精密度，20、400 和 800ng/mL 时的变异系数分别为 1.65%、1.86%和 1.26%。通过这种简单的方法，实现了拉氏囊素 A 的出色分离和灵敏度，从而能够快速分析血浆样品，用于吸收、分布和代谢研究。
