Abstract

Tris(4-chlorophenyl)methane (TCPMe) is a byproduct of dichlorodiphenyltrichloroethane synthesis. TCPMe and its metabolite tris(4-chlorophenyl)methanol (TCPMOH) are environmentally prevalent and have been detected in wildlife and humans. Due to inadequate data addressing its toxicity, the National Toxicology Program (NTP) is testing TCPMe in Hsd:Sprague Dawley SD (HSD) rats following perinatal exposure. In support of the toxicology studies, a gas chromatography – mass spectrometry (GC-MS) method was validated to simultaneously quantitate TCPMe and TCPMOH in male Sprague Dawley rat plasma (primary matrix) over calibration standard ranges of 2–200 ng/mL and 1–100 ng/mL, respectively. The method was linear (r² ≥ 0.9975), accurate (relative error (RE) ≤ ±12.8 (TCPMe) and ±14.5% (TCPMOH), and precise (relative standard deviation (RSD) ≤ 7.6 (TCPMe) and 3.8% (TCPMOH)). The limits of quantitation were 2 and 1 ng/mL and the limits of detection were 0.73 and 0.07 ng/mL for TCPMe and TCPMOH, respectively. Samples, as high as 2000 ng/mL for TCPMe (RSD ≤ 3.9, RE ≤ ±1.0) and 1000 ng/mL for TCPMOH (RSD ≤ 1.0, RE ≤ ±2.9), were successfully diluted with plasma into the validated concentration range. The method was selective and both TCPMe and TCPMOH were quantified in all secondary matrices (HSD male and female plasma, gestation day (GD)18 plasma, amniotic fluid, and fetus, postnatal day (PND)4 dam and pup plasma) using a primary matrix curve (RE ≤ ±14.4% and 11.5; RSD ≤ 7.6 and 11.8%, respectively). These results demonstrate that the method is suitable for simultaneous quantitation of TCPMe and TCPMOH in rodent plasma and fetuses for the evaluation of gestational and lactational transfer following perinatal exposure of TCPMe in NTP studies.

摘要

三（4-氯苯基）甲烷（TCPMe）是二氯二苯基三氯乙烷合成的副产物。TCPMe 及其代谢物三（4-氯苯基）甲醇 (TCPMOH) 在环境中普遍存在，并已在野生动物和人类中检测到。由于解决其毒性的数据不足，国家毒理学计划 (NTP) 正在围产期暴露后在 Hsd:Sprague Dawley SD (HSD) 大鼠中测试 TCPMe。为支持毒理学研究，验证了一种气相色谱-质谱 (GC-MS) 方法，可在 2–200 ng/mL 和 1 的校准标准范围内同时定量雄性 Sprague Dawley 大鼠血浆（初级基质）中的 TCPMe 和 TCPMOH –100 纳克/毫升，分别。该方法是线性的（r ²≥ 0.9975），准确（相对误差（RE）≤±12.8（TCPMe）和±14.5％（TCPMOH），精确（相对标准偏差（RSD）≤7.6（TCPMe）和3.8％（TCPMOH））。 TCPMe 和 TCPMOH 的定量分别为 2 和 1 ng/mL，检测限分别为 0.73 和 0.07 ng/mL。TCPMe 的样品高达 2000 ng/mL (RSD ≤ 3.9, RE ≤ ±1.0) 和 1000 ng/mL 的 TCPMOH (RSD ≤ 1.0, RE ≤ ±2.9) 用血浆成功稀释到验证的浓度范围。该方法具有选择性，在所有二级基质（HSD 男性和女性血浆、妊娠使用初级矩阵曲线（RE ≤ ±14.4% 和 11.5；RSD 分别为 7.6 和 11.8%）。这些结果表明，该方法适用于啮齿动物血浆和胎儿中 TCPMe 和 TCPMOH 的同时定量，用于评估 NTP 研究中围产期暴露 TCPMe 后的妊娠和哺乳期转移。