Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, ON, K1A 0K9, Canada.
Centre de Toxicologie du Québec (CTQ), Institut national de santé publique du Québec (INSPQ), Québec, QC, G1V 5B3, Canada.
Chemosphere. 2023 Oct;338:139603. doi: 10.1016/j.chemosphere.2023.139603. Epub 2023 Jul 20.
Phthalates are non-persistent chemicals measured as metabolites in urine. Over time, new metabolites have been identified. In the original Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured 11 phthalate metabolites in first trimester urine samples. The goal of the present study was to develop a method to measure new metabolites, to increase the sensitivity for some previously measured metabolites, and to measure these new metabolites in biobanked urine samples from MIREC participants. Using Ultra Performance Liquid Chromatography with a tandem mass spectrometer, we developed a method to measure 24 metabolites from 10 different parent phthalates. Chromatographic interpretation of some of the di-iso-decyl phthalate metabolites (mono-(2-propyl-6oxoheptyl) phthalate (MOiDP), mono-(2,7-methyl-7-carboxyheptyl) phthalate (MCiNP), mono-(2-propyl-6-hydroxy-heptyl) phthalate (MHiDP)) and di-iso-nonyl phthalate metabolites (mono(oxo-isononyl) phthalate (MOiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxy-isononyl) phthalate (MHiNP) and mono-isononyl phthalate (MiNP)) was challenging as these are complex isomeric mixtures. To validate and confirm our quantitation peaks, an assay using a high-resolution detection technique was developed on a Quadrupole Time-of-Flight (QToF) system. This system has a mass resolution of at least 0.005 amu, compared to 0.5 amu for the MS/MS detector. Using the QToF system, the distinction between an isomer and possible interference was achieved with the use of the exact mass. In about 1800 MIREC samples, mono-cyclo-hexyl phthalate (MCHP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), mono-iso-decyl phthalate (MiDP), and mono-n-octyl phthalate (MnOP) were rarely detected, while detection of MMP was improved. MCiOP, MiNP and MCiNP had to be reported semi-quantitatively. Given the complexity of isomeric mixtures of some phthalates, researchers must be careful in their determination of the analytes and the approach used in their quantification when generating biomonitoring data. This study produced biomonitoring data for a large population of pregnant people that can be used in risk assessment of phthalates. Future work will examine associations with birth and child outcomes.
邻苯二甲酸酯是非持久性化学物质，可作为尿液中的代谢物进行测量。随着时间的推移，已经发现了新的代谢物。在最初的母婴环境化学物质研究（MIREC）研究（2008-2011 年）中，我们测量了 11 种邻苯二甲酸酯代谢物在妊娠早期的尿液样本中。本研究的目的是开发一种测量新代谢物的方法，提高一些先前测量代谢物的灵敏度，并测量 MIREC 参与者的生物库尿液样本中的这些新代谢物。使用超高效液相色谱与串联质谱，我们开发了一种从 10 种不同母体邻苯二甲酸测量 24 种代谢物的方法。一些二异壬基邻苯二甲酸酯代谢物（单-（2-丙基-6-氧庚基）邻苯二甲酸酯（MOiDP），单-（2,7-甲基-7-羧基庚基）邻苯二甲酸酯（MCiNP），单-（2-丙基-6-羟基庚基）邻苯二甲酸酯（MHiDP））和二异辛基邻苯二甲酸酯代谢物（单（氧代异壬基）邻苯二甲酸酯（MOiNP），单（羧基异辛基）邻苯二甲酸酯（MCiOP），单（羟基异壬基）邻苯二甲酸酯（MHiNP）和单异壬基邻苯二甲酸酯（MiNP））的色谱解释具有挑战性，因为这些都是复杂的异构体混合物。为了验证和确认我们的定量峰，我们在四极杆飞行时间（QToF）系统上开发了一种使用高分辨率检测技术的测定方法。该系统的质量分辨率至少为 0.005amu，而 MS/MS 检测器的质量分辨率为 0.5amu。使用 QToF 系统，通过使用精确质量实现了异构体和可能干扰之间的区分。在大约 1800 个 MIREC 样本中，单环己基邻苯二甲酸酯（MCHP），单（7-羧基-正庚基）邻苯二甲酸酯（MCHpP），单异壬基邻苯二甲酸酯（MiDP）和单正辛基邻苯二甲酸酯（MnOP）很少被检测到，而 MMP 的检测得到了改善。MCiOP、MiNP 和 MCiNP 必须进行半定量报告。鉴于一些邻苯二甲酸酯的异构体混合物的复杂性，研究人员在生成生物监测数据时，必须谨慎确定分析物及其定量方法。本研究为大量孕妇提供了生物监测数据，可用于邻苯二甲酸酯的风险评估。未来的工作将研究与出生和儿童结局的关联。
