G/CMS同时检测人尿中N,N-二甲基乙酰胺及其代谢产物N-甲基乙酰胺

目的:探讨利用气相色谱-质谱(GC/MS)建立一种准确可靠的尿样中的N,N-二甲基乙酰胺(DMAC)及其代谢产物N-甲基乙酰胺(NMAC)的测定方法。方法:尿样经乙酸乙酯萃取、浓缩后,用GC/MS全扫描模式(scan)进行定性分析,确定组分出峰时间和特征质量离子,DMAC选择15、44、87m/z,NMAC选择30、43、73m/z,进行选择离子扫描(SIM),作定量分析。结果:DMAC和NMAC的线性范围分别为0.1 mg/L~10.0 mg/L和0.5 mg/L~10.0 mg/L;相关系数分别为0.9993和0.9991;最低检出限分别为0.02 mg/L和0.10 mg/L;相对标准偏差分别为3.26%和7.22%;样品加标回收率分别为91%~99%和88%~102%。结论:方法准确性好、灵敏度高、干扰少,是检测尿样中DMAC和NMAC的较好方法。     

尿中N,N-二甲基乙酰胺及其代谢物N-甲基乙酰胺的气相色谱测定法

目的:建立职业工人尿样中的N,N-二甲基乙酰胺(DMAC)及其代谢产物N-甲基乙酰胺(NMAC)的气相色谱测定方法。方法:尿样经冻融后离心,上清液加甲醇(1∶1,v/v)后用HP-INNOWAX毛细管柱分离,氢火焰离子化检测器(FID)对尿样进行检测,外标法定量。结果:DMAC和NMAC在0μg/ml～300.0μg/ml内呈线性关系;相关系数为0.9999;最低检出限分别为1.65μg/ml和2.90μg/ml;样品加标回收率分别为99.8%～100.4%和98.0%～99.9%。结论:该法操作简便、快速、准确、灵敏度高,适用于职业工人尿样中DMAC、NMAC的同时测定。     

尿中N-甲基乙酰胺直接进样-氮磷检测气相色谱分析法

目的 建立直接进样-气相色谱法检测尿中N-甲基乙酰胺(NMAC),为研制职业接触二甲基乙酰胺生物限值提供配套检测方法.方法 用甲醇稀释经冷冻离心的尿样,分离蛋白沉淀后直接进样,经聚乙二醇毛细管色谱柱程序升温分离,氮磷检测器检测.结果 尿中NMAC的线性范围为1.0～250 mg/L,相关系数为1.0000;最低检测浓度为0.2 mg/L;添加水平为10.58、52.90、211.60 mg/L时,NMAC回收率为96.0％～99.4％,平均回收率为97.8％;批内和批间相对标准偏差为1.5％～3.4％.结论 本方法简便快速,灵敏准确,适用于DMAC职业暴露人群尿样中NMAC的监测.     

职业接触二甲基乙酰胺工人尿中甲基乙酰胺生物限值研究

目的 研制我国职业接触二甲基乙酰胺(DMAC)工人尿中甲基乙酰胺(NMAC)的生物限值.方法 选择3家氨纶生产企业201名接触DMAC工人,应用个体采样器采集工作周末工作日的车间空气样品,用气相色谱法检测个体DMAC接触水平,同时收集当日工人班末尿样,应用气相色谱法测定尿中NMAC浓度以评价DMAC接触工人内暴露水平.通过内外剂量的回归方程、百分位数和相对内暴露(RIE)指数计算,推荐我国职业接触二甲基乙酰胺工人尿中NMAC生物接触限值.结果 201名DMAC接触工人中接触浓度符合我国DMAC接触限值133名,占66.2％,接触浓度范围在0.40～300.12mg/m3,几何平均浓度为19.4 mg/m3.工作周末班未尿中NMAC浓度范围为1.30～189.42 mg/g Cr,几何平均浓度为23.7 mg/g Cr.尿中NMAC浓度与个体DMAC外暴露浓度有相关性(F=188.872,R2=0.487,P＜0.001),回归方程为log(NMAC mg/g Cr)=0.685+0.455 log(DMAC mg/m3).以我国DMAC职业接触限值PC-TWA为20 mg/m3推算,尿中NMAC浓度为18.92 mg/g Cr.当工作场所空气中DMAC＜20 mg/m3时,90％的工人尿中NMAC水平为23.9 mg/g Cr.按RIE指数推算的尿中NMAC为19.0 mg/g Cr.结论 参考国外DMAC生物接触限值标准,建议我国DMAC生物接触限值为工作周末班未尿中NMAC 20 mg/g Cr.     

二甲基乙酰胺职业接触及与尿中甲基乙酰胺的关系

[目的]探讨职业二甲基乙酰胺（DMAC）接触与尿中甲基乙酰胺（NMAC）的相关性。[方法]对3家氨纶生产企业6个工种201名工人进行空气中DMAC暴露浓度监测及工作周末班末尿样采集,同时对20名纺丝工连续一周空气样品和班末尿样的采集;分别用气相色谱测定空气中DMAC和尿中NMAC含量。[结果]氨纶生产过程中组件清洗工、纺丝工接触DMAC水平最高（P〈0.0033）,中位数分别为32.10、22.02mg/m3,其尿中NMAC浓度较其他工种高（P〈0.0033）,中位数分别为30.09、22.72mg/gCr;工作周末班末尿NMAC含量与空气中DMAC浓度呈直线相关,直线方程为log（U-NMAC）=0.685＋0.455×log（A-DMAC）（r=0.698,P=0.001）;长期DMAC接触者,接触2d后尿中NMAC呈较高水平（P〈0.0033）;个体DMAC接触代谢转化为NMAC的相对内暴露指数（RIE）与DMAC接触浓度呈负相关（rs=-0.781,P=0.001）。[结论]工作周末班末尿NMAC含量与空气中DMAC浓度呈良好对数线性关系。     

液液萃取气相色谱法测定尿中4种酰胺类化合物

目的 建立同时测定尿中N,N-二甲基甲酰胺（N,N-dimethylformamide,DMF）、N,N-二甲基乙酰胺（N,Ndimethylacetamide,DMAC）、N-甲基甲酰胺（N-methylformamide,NMF）和N-甲基乙酰胺（N-methylacetamide,NMAC）的液液萃取-气相色谱法。方法 取10.0 mL尿样，加入3.6 g NaCl溶解，再加入2.0 mL异丁醇进行涡旋萃取，经毛细管柱HP-Innowax(30 m×0.32 mm×0.50μm)分离，氮磷检测器检测。结果 4种待测物浓度在0.20～50.0μg/mL范围内线性关系良好，相关系数r在0.999 5～0.999 9之间。检出限范围0.02～0.04μg/mL，定量下限范围0.08～0.20μg/mL；在空白尿样中添加0.5、10.0、40.0μg/mL 3个水平的混合标准溶液时，各待测物的回收率为92.0%～104%，相对标准偏差为2.2%～6.6%；尿液在-18℃条件下至少可放置14 d。结论 建立的尿中4种酰胺类测定方法灵敏度高、准确可靠，适用于职业工人尿样中DMF、DMAC、N...     

GC/MS法同时检测尿中N,N-二甲基甲酰胺及其代谢产物N-甲基甲酰胺

尿样中的N,N-二甲基甲酰胺（DMF）及其代谢产物N-甲基甲酰胺（NMF）用醋酸乙酯萃取、浓缩后,用气相色谱-质谱联用仪分析,全扫描模式（scan）进行定性分析,确定组分出峰时间和特征质量离子,然后选取30.0、59.0、440、73.0m/z进行选择离子扫描（SIM）,作定量分析。DMF和NMF的线性范围分别为0.2～48.0mg/L和0.5～50.0mg/L;相关系数分别为0.998和0.999;最低检出限分别为0.05mg/L和0.15mg/L;相对标准偏差分别为4.0％～6.4％和5.1％～8.4％;样品加标回收率分别为91.1％～97.0％和88.8％～96.3％;样品在4℃的冰箱内至少可保存2周。方法准确性好。灵敏度高、干扰少。是检测尿样中DMF和NMF的较好方法。     

二甲基乙酰胺对工人健康的影响

目的 探讨二甲基乙酰胺( DMAC)肝脏毒性的特点及其接触指标.方法 采用分层抽样法选择145名研究对象,对研究对象进行问卷调查和健康检查等,并进行工作场所空气监测,同时采集研究对象每天的班末尿样或者工作周周末班末尿样,并对工作场所空气中DMAC浓度、尿中甲基乙酰胺(NMAC)进行相关回归分析.结果 卷绕岗位空气中DMAC浓度较高,其他岗位工作场所空气中浓度较低;肝功能异常18例,检出率为12.4％,11例(61.1％)发生在接触DMAC第1年内,且主要集中在卷绕岗位;尿中NMAC浓度与空气中DMAC浓度相关(r=0.44,P＜0.01).结论 DMAC短期接触即可造成工人肝功能异常,尿中NMAC可作为DMAC的接触指标.     

高效液相色谱法测定尿中N-乙酰-S-(N-甲基甲氨酰)半胱氨酸的含量

目的:建立简便有效的测定尿中N-乙酰-S-(N-甲基甲氨酰)半胱氨酸(AMCC)的高效液相色谱方法。方法:尿样经固相萃取后用高效液相色谱法分析,采用C18柱,以5%乙腈水溶液为流动相,流速1.0 ml/min,检测波长为196 nm。结果:尿中AMCC在1.00 mg/L～50.00 mg/L浓度范围内线性关系良好,相关系数为1.0000。方法精密度为2.8%～4.0%,检出限为0.1 mg/L,加样回收率为86.2%～96.1%。结论:该方法各项性能指标均符合职业卫生标准制定指南第5部分:生物材料中化学物质测定方法中相关要求,可用于测定二甲基甲酰胺(DMF)暴露工人尿中的AMCC含量。     

职业接触二甲基甲酰胺人群尿中甲基甲酰胺水平研究

选择二甲基甲酰胺(dimethylformamide,DMF)职业接触人群99人,不接触DMF及其他有机溶剂的人员22人,测定尿中甲基甲酰胺(NMF)水平。比较DMF职业接触人群不同车间、DMF接触水平、工种、年龄、性别等因素对尿中NMF水平的影响。结果显示,随着DMF职业接触水平的增加,尿中NMF浓度明显升高(P0.01)。尿中NMF可作为反映DMF职业接触的生物监测标志物。     

Biological monitoring of workers exposed to<Emphasis Type="Italic"> N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylformamide in synthetic leather manufacturing factories in Korea

Objectives To investigate the relationship between N,N-dimethylformamide (DMF) exposure and excretion of urinary N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) and N-methylformamide (NMF) in workers at synthetic leather manufacturing factories in Korea, for the first time.Methods One-hundred forty-four male workers at nine synthetic leather manufacturing factories were surveyed. Exposure to DMF was evaluated through breathing zone air sampling followed by analysis via a gas chromatograph equipped with a flame ionization detector (GC-FID). The levels of NMF and AMCC were determined by a GC with a flame thermionic detector (GC-FTD). Urine samples were collected at the end of the workshift.Results and Conclusions Geometric mean of workplace air DMF and urinary NMF was 8.8 ppm and 47.5 mg/l, respectively, and the level of DMF and NMF was significantly correlated. The biological exposure limit for NMF (15 mg/ml) was exceeded in 89.5% of urine samples, and 37.9% of air samples exceeded the environmental DMF exposure limit (10 ppm), indicating a serious health risk to the employees of the synthetic leather industry in Korea. Exposure to 10 ppm DMF in the workplace air corresponded to a urinary NMF concentration of 53.4 mg/l. Alcohol intake the day before urine was sampled influenced NMF excretion into urine (40.5 mg/l NMF for the no-alcohol group and 94.6 mg/l for the group consuming more than 63.0 g alcohol/day). We could not find a significant relationship between air DMF and urinary AMCC concentration. Exposure to 10 ppm DMF corresponded to an AMCC concentration of 8.0 mg/l in the urine samples collected on the same day as the air was sampled.     

Determination of bromide ion concentration in urine using a head-space gas chromatography and an ion chromatography--biological monitoring for methyl bromide exposure

A head-space gas chromatography (GC) and an ion chromatography coupled with a conductive detector (IC) were used to evaluate levels of bromide ion in urine. The GC method followed by methylation with dimethyl sulfate, showed higher accuracy (2.7% of relative standard deviation) and lower minimum detection limit (0.4 mg/l) compared to the IC procedure of those values which were 8.7% and 1.0 mg/l. The correlation coefficient between the analytical results of 15 urinary samples by the two methods was 0.793. The bromide ion concentrations detected in 36 urine samples of workers exposed to methyl bromide were averaged at 13.3 +/- 7.7 mg/l. The average bromide ion of the non-exposed group was 7.1 +/- 2.1 mg/l (n = 6). Exposed methyl bromide concentrations of workers were monitored with passive samplers during their work shifts (8 hr). No significant correlation between exposed methyl bromide and bromide ion concentrations in urine was observed.     

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry

Objectives: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans.Methods: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. Results and conclusions: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range <0.1–159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (<1.0–108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from <0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2  days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity. Received: 25 June 1999 / Accepted: 2 October 1999     

Phthalic acid excretion as an indicator of exposure to phthalic anhydride in the work atmosphere

Summary The concentration of phthalic acid was determined in the urine of nine subjects occupationally exposed to phthalic anhydride. For the determination, the urine samples were acidified, extracted with dimethyl ether, esterified with boron trifluoride/methanol and measured by electron capture gas chromatography. Environmental air samples were collected in Tenax tubes, eluted with methyl-t-butyl ether and assayed by electron capture gas chromatography. Significant correlations were found between the concentration in urine samples (range: 0.3–14.0 mol/mmol creatinine), collected at different times of the day, and the time-weighed average atmospheric concentrations (range: 0.03–10.5 mg/m³). No conjugation of phthalic acid in the urine was observed. The detection limit for urine samples (10 ml) was 0.05 mol/l) and that for air samples 0.4 g/m³. The method has potential for biological monitoring of workers exposed to phthalic anhydride. It was found that at atmospheric anhydride concentrations of about 30% of the hygienic reference value (6 mg/m³). which is applied in many market economies, a body-burden was caused which was not eliminated overnight.     

测定尿中三氯乙酸的自动顶空气相色谱法

目的建立尿中三氯乙酸的自动顶空气相色谱测定方法。方法尿中的三氯乙酸加热脱羧生成三氯甲烷,经自动顶空进样器进样,解吸后进气相色谱分离,FID检测,外标法定量。结果三氯乙酸在0.1～100mg/L浓度范围内线性良好(r0.999),最低检出浓度为0.02 mg/L(v=5 ml),方法准确度高,重现性好,样品加标回收率为98.6%～99.7%,相对标准偏差(RSD)为0.8%～2.6%。结论该法简便、灵敏、准确,适用于三氯乙烯接触人群尿三氯乙酸的检测。     

Dermal absorption of N,N-dimethylacetamide in human volunteers

Objectives: We investigated the potential for the dermal absorption of N,N-dimethylacetamide (DMAC: CAS No. 127-19-5) vapor, the biological half-life of N-methylacetamide (NMAC) in urine as the biological exposure item of DMAC, and the adjustment method for urinary concentrations. Methods: Twelve healthy male volunteers (mean age 25.2 years, range 21–43 years) were exposed to DMAC for 4 h on two occasions at intervals of 96 h or above. Each volunteer sat inside a whole-body-type exposure chamber for the dermal exposure experiment or outside the chamber for the inhalation exposure experiment. The temperature and relative humidity in the chamber were controlled at approximately 26 °C and 40% in order to keep the skin (90% naked) of the volunteers dry. DMAC concentrations were 6.1 ± 1.3 ppm for dermal exposure and 6.1 ± 1.3 ppm for inhalation exposure. Urine samples were collected from 0 h through 36 h and at 48 h and 72 h after the exposure. Extrapolations from exposure concentrations for 4 h to 10 ppm for 8 h were performed. Results: Mean dermal absorption was estimated to be 40.4% of the total DMAC uptake. The biological half-lives of urinary NMAC were 9.0 ± 1.4 h and 5.6 ± 1.3 h via skin and lung, respectively. Mean NMAC in urine just after 5 consecutive workdays (8 h/day) at 10 ppm DMAC exposure was assumed to be 33.7 mg/g · Cr (18.6–70.0 mg/g · Cr). Creatinine-adjusted NMAC concentration in urine for each volunteer within 12 h after the exposure was more closely correlated with the total excretion amount of NMAC up to 36 h than with urinary-volume-adjusted or specific-gravity-adjusted NMAC concentration in both the dermal and inhalation exposure experiments. Conclusions: DMAC vapor was significantly absorbed through the skin. Estimated NMAC values indicate that 20 mg/g · Cr NMAC seems to be appropriate as the biological exposure index. Received: 6 August 1999 / Accepted: 9 September 1999     

Urinary determination of N-acetyl- S-( N-methylcarbamoyl)cysteine and N-methylformamide in workers exposed to N,N-dimethylformamide

OBJECTIVES: We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (NMF) (mainly from N-hydroxy- N-methylformamide) and N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC), and levels of exposure to N, N-dimethylformamide (DMF) among occupationally exposed subjects. METHODS: Exposure levels were determined by personal sampling: breathing zone air samples were collected by means of passive samplers. DMF collected by the charcoal in personal samplers was analysed after extraction with methanol by a gas chromatograph. For the purpose of biological monitoring the levels of NMF and AMCC were measured in pre-shift and post-shift samples. Determinations were carried out by, respectively, gas chromatography and high performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: The mean time-weighted average (TWA) exposure was approximately half (13.5 mg/m(3)) of the current threshold limit value, the range of the values was from 0.4 to 75.2 mg/m(3). Environmental DMF concentrations exhibited a significant correlation with the specific mercapturic acid (AMCC) collected at the end of the working week (AMCC Friday morning mg/l=1.384xDMF (mg/m(3))+8.708; r(2)=0.47; P<0.008]; hence urinary AMCC represents an index of the average exposure during several preceding working days, making it possible to calculate the approximate relationship between DMF uptake and excretion of this metabolite. A significant correlation was found also between the daily excretion of NMF and the corresponding levels of DMF in air. The equation of the regression line was: NMF (mg/g creatinine)=0.936xDMF (mg/m(3))+7.306; r(2)=0.522 ( P<0.0001).     

柱前衍生-液液微萃取-毛细管气相色谱法测定尿碘

目的:建立尿中碘化物的液-液萃取毛细管气相色谱测定方法。方法:尿碘经衍生成易气化衍生物,通过有机溶剂萃取、离心,直接吸取有机层进样,经气相色谱分离,电子捕获检测器定量检测。结果:该法分离效果好,检出限为0.05μg/L,加标回收率为95.2%～98.6%,相对标准偏差(RSD)为1.0%～2.5%。结论:该方法简单,灵敏度高,可用于尿样中碘的测定。     

分子印迹固相萃取-高效液相色谱法测定尿液中甲基苯丙胺和苯丙胺

目的:建立快速、准确的尿液中甲基苯丙胺(MA)及其代谢产物苯丙胺(AMP)的分子印迹固相萃取(MISPE)高效液相色谱测定方法。方法:尿液与10 mmol/L醋酸铵缓冲液(pH 8.0)混合后离心分离(8000 rpm),采用预先活化过的分子印迹固相萃取柱净化,以醋酸/乙腈溶液洗脱,在XBridge RP18色谱柱上,以甲醇-乙腈-水溶液(15∶30∶55,V/V/V)为流动相,采用210 nm波长进行检测。结果:MA和AMP的加标回收率在88.5%～97.0%范围,其相对标准偏差均小于5.0%,在0.05 mg/L～15.0 mg/L范围呈现良好的线性,其回归系数大于0.999,检出限(LODs)分别为0.005 mg/L和0.01 mg/L。结论:本方法回收率高,净化效果显著,稳定性好,杂质干扰少,可满足临床吸毒病人尿液中MA和AMP的检测要求。