Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jun 1;879(19):1551-6. doi: 10.1016/j.jchromb.2011.03.046. Epub 2011 Mar 31.
In this study, a method using liquid chromatography triple quadrupole mass spectrometry (LC/MS/MS) is described for the analysis of the plant growth regulator chlormequat (CCC) in human urine. Analysis was carried out using selected reaction monitoring (SRM) in the positive ion mode. [(2)H(4)] labeled CCC as internal standard (IS) was used for quantification of CCC. The limit of detection (LOD) was determined to 0.1 ng/mL. The method was linear in the range 0.3-800 ng/mL urine and had a within-run precision of 4-9%. The between-run precision was determined at urine levels of 7.0 and 31 ng/mL and found to be 5 and 6% respectively. The reproducibility was 3-6%. To validate CCC as a biomarker of exposure, the method was applied in a human experimental oral exposure to CCC. Two healthy volunteers received 25 μg/kg b.w. CCC in a single oral dose followed by urine sampling for 46 h post-exposure. The CCC was estimated to follow a first order kinetic and a two compartment model with an elimination half-life of 2-3h and 10-14 h respectively. One hundred 24h urine samples were collected from non-occupationally exposed individuals in the general population in southern Sweden. All samples had detectable levels above the LOD 0.1 ng/mL urine. The median levels were 4 ng/mL of CCC in unadjusted urine. The levels found in the population samples are several magnitudes lower than those found in the experimental exposure, which corresponds to an oral exposure of 50% of the ADI for CCC.
本研究描述了一种使用液相色谱三重四极杆质谱（LC/MS/MS）分析植物生长调节剂矮壮素（CCC）在人尿中的方法。分析采用正离子模式下的选择反应监测（SRM）进行。[(2)H(4)]标记的 CCC 作为内标（IS）用于定量 CCC。检测限（LOD）确定为 0.1ng/mL。该方法在 0.3-800ng/mL 尿范围内呈线性，批内精密度为 4-9%。在 7.0 和 31ng/mL 的尿水平下测定批间精密度，分别为 5%和 6%。重现性为 3-6%。为了验证 CCC 作为暴露生物标志物的有效性，该方法应用于人体口服暴露于 CCC 的实验中。两名健康志愿者接受了 25μg/kg bw 的 CCC 单次口服剂量，随后在暴露后 46 小时内采集尿液。CCC 被估计遵循一级动力学和双室模型，消除半衰期分别为 2-3h 和 10-14h。在瑞典南部的一般人群中，从 100 名非职业暴露个体中采集了 24 小时尿液样本。所有样本的检测水平均高于 LOD 0.1ng/mL 尿。未调整尿液中 CCC 的中位数水平为 4ng/mL。在人群样本中发现的水平远低于实验暴露中发现的水平，这相当于 CCC 的 ADI 的 50%口服暴露。
