Biological monitoring of isocyanates and related amines

Summary Two men were exposed to toluene diisocyanate (TDI) atmospheres at three different air concentrations (ca. 25, 50 and 70g/m³) . The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m³ stainless-steel test chamber. The effective exposure period was 4h. The isomeric composition of the air in the test chamber was 30% 2,4-TDI and 70% 2,6-TDI. The concentration of TDI in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma and urine, the related amines, 2,4-toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas chromatography using selected ion monitoring (SIM) in the electron-impact mode. In plasma, 2,4- and 2,6-TDA showed a rapid-phase elimination half-time of ca. 2–5 h, and that for the slow phase was > 6 days. A connection was observed between concentrations of 2,4- and 2,6-TDI in air and the levels of 2,4- and 2,6-TDA in plasma. The cumulated amount of 2,4-TDA excreted in the urine over 24 h was ca. 15%–19% of the estimated inhaled dose of 2,4-TDI, and that of 2,6-TDA was ca. 17%–23% of the inhaled dose of 2,6-TDI. A connection was found between the cumulated (24-h) urinary excretion of 2,4- and 2,6-TDA and the air concentration of 2,4- and 2,6-TDI in the test chamber. A connection was also observed between the rate of urinary excretion of 2,4- and 2,6-TDA over the last 2h of exposure and the air concentration of 2,4- and 2,6-TDI in the test chamber. Biological monitoring of exposure to monomeric 2,4- and 2,6-TDI by the analysis of 2,4- and 2,6-TDA in biological media is feasible. A method based on 24-h urine sampling and determination levels of 2,4- and 2,6-TDA in hydrolysed urine is recommended. However, exposure to TDI is often associated with aerosols containing polymeric TDI, and we do not know whether analysis of TDA in urine can also be used as a marker of exposure to TDI prepolymers.     

山茨菇挥发油化学成分气相色谱-质谱联用分析

目的：分析山茨菇挥发油的化学成分。方法：用气相色谱-质谱联用法（GC-MS）分析。结果：山茨菇挥发油的化学成分，共鉴定了40个组分，其中芒樟醇、异石竹烯、β-金合欢烯、橙花叔醇、细辛醚、肉桂酸酯类等为其挥发油主要成分。结论：该结果可供临床研究参考。     

Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) methods were developed and validated for the evaluation of motexafin lutetium (MLu, lutetium texaphyrin, PCI-0123) pharmacokinetics in human plasma. The LC-MS/MS method was specific for MLu, whereas the ICP-AES method measured total elemental lutetium. Both methods were fast, simple, precise, and accurate. For the LC-MS/MS method, a closely related analogue (PCI-0353) was used as the internal standard (IS). MLu and the IS were extracted from plasma by protein precipitation and injected onto and LC-MS/MS system configured with a C18 column and an electrospray interface. The lower limit of quantitation was 0.05 μg MLu mL⁻¹, with a signal-to-noise ratio of 15∶1. The response was linear from 0.05 to 5.0 μg MLu mL⁻¹. For the ICP-AES method, indium was used as the IS. The sample was digested with nitric acid, diluted, filtered, and then injected onto the ICP-AES system. Two standard curve ranges were validated to meet the expected range of sample concentrations: 0.5 to 50, and 0.1 to 10 μg Lu mL⁻¹. The LC-MS/MS and ICP-AES methods were validated to establish accuracy, precision, analyte stability, and assay robustness. Interday precision and accuracy of quality control samples were ≤6.3% coefficient of variation (CV) and within 2.2% relative error (RE) for the LC-MS/MS method, and ≤8.7% CV and within 4.9% RE for the ICP-AES method. Plasma samples from a subset of patients in a clinical study were analyzed using both methods. For a representative patient, over 90% of the elemental lutetium in plasma could be ascribed to intact MLu at early time points. This percentage decreased to 59% at 48 hours after dosing, suggesting that some degradation and/or metabolism of the drug may have occurred.     

GC—MS对蓝桉果实及大叶桉果实挥发油成分研究

目的:用气相色谱-质谱法对蓝桉果实和大叶桉果实挥发性成分进行研究。方法:采用水蒸气蒸馏法从2种中药中提取挥发油,然后经毛细管色谱柱进行分离,用归一化法计算含量。色谱条件:DB-WAX石英毛细管柱(30 m×0.32mm,0.25μm),柱温条件:起始温度40℃(3 min)5℃·min-1 250℃(10 min),MS检测器,进样量1μL,载气He(1.0 mL·min-1)。质谱分析条件:电离方式为EI,离子源温度200℃,电子能量70 eV。结果:蓝桉果实挥发油中鉴定出31个成分,大叶桉果实中鉴定出34个成分,两者指纹谱存在较大差异。结论:本法可靠,可用于2种果实化学成分的鉴别。     

密花石斛的HPLC/UV/MS指纹图谱研究

目的 采用HPLC／UV／MS法对密花石斛进行指纹图谱研究。方法 采用Agilent Zorbax SB—C18柱；甲醇和水为流动相进行梯度洗脱；流速为1．0mL／min。结果 得到分离度较好的密花石斛HPLC／UV指纹图谱，标示了9个共有峰，并用HPLC／MS对其部分色谱峰进行了初步定性。结论 该方法可用于密花石斛指纹图谱的测定，并为其全面质量控制提供参考。     

高效液相色谱—电喷雾质谱法同时测定人血浆中咖啡因、咪哒唑仑和代谢产物及其在药物代谢研究中的应用

目的:建立高效液相色谱-电喷雾质谱法同时测定人体血浆中咖啡因及代谢物1,7-二甲基黄嘌呤、咪哒唑仑及代谢产物1-羟咪哒唑仑。并将它应用于中药止咳橘红颗粒对CYP3A4和CYP1A2抑制作用的研究。方法:血浆样品先经液-液萃取纯化浓缩后,以ODS-C18为固定相,甲醇-0.01％甲酸不同比例为梯度洗脱流动相,内标物为阿普唑仑。经HPLC分离后的化合物在电喷雾离子源中被电离,电离后以选择离子方式检测各化合物的分子离子峰,以峰的保留时间及质荷比进行定性,以峰面积进行定量。结果:咖啡因、1,7-二甲基黄嘌呤、咪哒唑仑、1-羟咪哒唑仑分别在50～5000 ng·mL-1(r=0.9971),22.4～2240 ng·mL-1(r=0.9982),1.23～123 ng·mL-1(r=0.9997),0.84～84 ng·mL-1(r=0.9983)的范围内呈良好的线性关系。4种化合物的平均回收率均大于90％,日内及日间RSD均小于10％。结论:此方法简便,快速,灵敏,可同时测定人体血浆中咖啡因、咪哒唑仑及各自的主要代谢产物。     

液相色谱-电喷雾质谱联用法测定人血浆中托吡酯

目的:建立测定人血浆中托吡酯的液相色谱-电喷雾质谱联用(LC/ESI-MS)法。方法:待测血浆0.2 mL经甲醇沉淀除去蛋白,离心,取上清液10μL在Diamonsil C18柱上分离,流动相为甲醇-2.5 mmol·L-1醋酸铵(80:20),流速0.4 mL·min-1,LC/ESI-MS选择离子检测,负离子模式,用于定量分析的离子分别为m/z338(托吡酯)和m/z 356(吲哚美辛,内标)。结果:血浆中无干扰测定的内源性物质,每个样品分析时间小于7 min;本法线性范围为40-2560 ng·mL-1,最低定量浓度为40 ng·mL-1;日内、日间RSD分别小于3.8％和13.4％,相对偏差小于5.9％。结论:该法操作简便、快速、准确、灵敏度高,适用于临床药物动力学研究。     

侧柏果实挥发油化学成分的研究

 目的:研究侧柏果实挥发油的化学成分。方法:采用水蒸汽蒸馏法提取侧柏果实挥发油;以气相色语-质谱( GC-MS)联用技术，对化学成分进行分离和鉴定。通过标准图谱对照确定化合物名称。以总离子流图归一化法测定其百分含量。结果:共分离出40多个峰，确证了其中34种成分，其含量占总离子流的92%以上。结论:侧柏果实挥发油的主要化学成分为a-雪松酯。     

柴胡超临界二氧化碳萃取物化学成分气相-质谱联用分析

目的：研究柴胡超临界CO2萃取物的化学成分。方法：应用气／质联用技术对柴胡超临界CO2萃取物进行分析。结果：从萃取物中分离并鉴定出11种化合物，其中主要组分为饱和及不饱和脂肪酸。含量占气化产物总量的96．2％。结论：本研究为柴胡的开发利用提供了实验依据。     

中药木鳖子中脂肪酸的气相色谱-质谱联用分析

目的：测定中药木鳖子中的脂肪酸成分。方法：以石油醚为溶剂，采用索氏提取法提取其脂肪酸。经甲酯化处理后，用GC／MS联用仪对其脂肪酸组成进行了分析和鉴定。结果：共分离出14种脂肪酸，占脂肪酸总量的89．23％。结论：木鳖子脂肪酸中不饱和脂肪酸占41．91％，且大部分是具生物活性物质。