HPLC测定PVC输液袋中的邻苯二甲酸二(2-乙基己基)酯

目的 测定PVC输液袋中增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)的含量.方法 采用HPLC法,流动相为甲醇-水(90:10),流速为1.0 ml·min-1,检测波长为222 nm.结果 峰面积与DEHP浓度的线性关系良好(r=0.9999).结论 所用方法简便,结果准确可靠.     

GC-MS法测定一次性使用静脉营养输液器中增塑剂DEHP的溶出量

目的:建立测定一次性使用静脉营养输液器中增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)溶出量的方法。方法:采用气相色谱-质谱联用(GC-MS)法,以邻苯二甲酸二丁酯为内标,使用一次性使用静脉营养输液器制备营养液,测定室温放置和模拟临床输液24 h后营养液中DEHP的溶出量。采用Rtx-5 MS色谱柱;进样口温度:300℃;载气:氦气;程序升温模式:起始温度200℃,15℃/min升温至280℃,维持5 min;EI离子源,离子源温度:250℃,接口温度:280℃;采集模式:选择离子监测模式(SIM):质荷比(m/z)149。结果:DEHP检测质量浓度的线性范围为0.2³0μg/m(lr=0.999 8),检测限为0.01μg/ml,定量限为0.04μg/ml,平均回收率为102.4%,RSD为4.23%(n=3),精密度试验RSD为2.7%(n=5)。室温放置24 h营养液中DEHP溶出量为0.54730μg/m(lr=0.999 8),检测限为0.01μg/ml,定量限为0.04μg/ml,平均回收率为102.4%,RSD为4.23%(n=3),精密度试验RSD为2.7%(n=5)。室温放置24 h营养液中DEHP溶出量为0.547¹7.400 mg,模拟临床输液24 h后营养液中DEHP溶出量为8.77917.400 mg,模拟临床输液24 h后营养液中DEHP溶出量为8.779¹0.620 mg,均小于成人的耐受摄入量(30 mg)。结论:本法简单、快速、准确,可用于一次性使用静脉营养输液器中DEHP溶出量的测定。     

PVC软输液袋对紫杉醇稳定性的影响及其中DEHP溶出量考察

目的考察聚氯乙烯(PVC)软输液袋对紫杉醇稳定性的影响及其中增塑剂邻苯二甲酸二(2-乙基)己酯(DEHP)的溶出情况。方法模拟临床使用紫杉醇的条件,用高效液相色谱法测定整个使用过程中紫杉醇的浓度变化和DEHP的溶出量。结果紫杉醇浓度随时间的延长而下降,DEHP的溶出量随温度的升高和时间的延长而增大。结论目前临床使用的紫杉醇配套输液袋绝大多数为PVC袋,由于紫杉醇浓度下降且溶出的DEHP可直接进入人体,不能保证用药安全,故应高度重视PVC软输液袋的危害性。     

静脉营养输液袋中DEHP的溶出量研究

目的:建立测定一次性使用静脉营养输液袋中增塑剂邻苯二甲酸二-(2-乙基己基)酯(DEHP)溶出量的方法。方法:采用气相色谱-质谱联用仪对一次性使用静脉营养输液袋DEHP溶出量进行定量分析,优化了色谱与质谱实验条件。结果:用该法测定出了一次性使用静脉营养输液袋DEHP溶出量小于3 mg.套-1。结论:本方法灵敏度高,重复性好,简便可行,可用于静脉营养输液袋的质量控制。     

医疗途径中增塑剂DEHP的溶出及其安全性研究概况

目的:为了解医疗途径中增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)的溶出及其对人体的安全性提供参考。方法:查阅相关文献,从DEHP的理化性质、毒性作用、溶出及体内药动学、各种医疗途径中人体的摄入量及耐受摄入量、目前国际上对含DEHP医疗器材的规定等方面进行分析。结果:DEHP易从聚氯乙烯医疗器材中溶出,进入人体后产生慢性毒性,毒性大小取决于摄入量和个体敏感性,其中新生儿接受全静脉营养、肠道营养、换血、体外心肺循环以及成人接受肠道营养、大量输血(外伤)、体外心肺循环、冠状动脉绕道、人工心脏移植等医疗途径时,会处于DEHP介导的不良反应的高风险中。结论:部分医疗途径中存在因DEHP释放使人体摄入量超过了耐受摄入量而产生危害的风险,应引起有关方面的高度重视。     

紫外分光光度法测定一次性使用体外循环管道中DEHP溶出量

目的建立测定一次性使用体外循环管道中邻苯二甲酸二（2-乙基己基）酯（DEHP）溶出量的方法。方法以乙醇为溶剂，于37℃浸泡样品10h，在超声波水浴中提取30min，采用紫外分光光度法测定浸泡液中DEHP含量，测定波长为275nm。结果DEHP浓度在300～700μg／mL范围内与吸光度有良好的线性关系，方法的平均回收率为97．32％，RSD为0．02％-0．11％；一次性使用体外循环管道产品在乙醇中浸泡10h后DEHP的溶出量为48．7～61．8mg／g。结论该测定方法简单快速，结果准确可靠，重现性好，专属性强，可以满足一次性使用体外循环管道中DEHP溶出量的质量监控需求。     

HPLC法测定牛黄上清丸及其药包材中DEHP的含量

目的:建立牛黄上清丸及其药包材中邻苯二甲酸二(2-乙基己基)酯(DEHP)含量的高效液相色谱测定方法。方法:采用Shim-Pack VP-ODS(150 mm×2.0 mm,5μm)色谱柱,流动相甲醇-水(95∶5),流速1.0 mL.min-1,检测波长为245 nm,柱温为30℃。结果:方法定量限0.1μg·mL-1,线性范围为0.1～100μg·mL-1,其标准曲线方程A=5.21×103C+5.20×103,r=0.9998,加标回收率为99.20%～100.3%,RSD为0.35%。结论:对32批牛黄上清丸及其药包材测定,结果表明该本方法操作简便,灵敏准确,能够满足牛黄上清丸(NSP)及其药包材(MPM)中DEHP含量的测定的需要,具有一定的应用价值。     

聚氯乙烯输液袋增塑剂的释出和对药物的吸附

聚氯乙烯（PVC）输液袋中使用较多的增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）在贮存和使用中会释出至输液中进入人体，药物也可能被PVC输液袋吸附。为此，本研究采用HPLC法测定了PVC输液袋中所释出DEHP的含量，两种PVC输液袋装不同介质后DEHP的释出量，不溶性微粒与DEHP的关系，以及PVC输液袋对硝酸甘油和地西泮的吸附。     

克林霉素磷酸酯注射液对一次性输液器中邻苯二甲酸二（2-乙基）己酯的溶出研究

摘要：目的:考察克林霉素磷酸酯注射液对一次性使用输液器中苯二甲酸二（2-乙基）己酯（DEHP）的溶出规律。方法:模拟临床使用克林霉素磷酸酯注射液经一次性输液器静脉滴注,UPLC-MS/MS法测定流出液中DEHP的溶出量。同时考察药物浓度和滴注时间对于DEHP溶出的影响,确定克林霉素磷酸酯注射液促进DEHP溶出的因素。结果:克林霉素磷酸酯注射液中的苯甲醇是促进一次性输液器中DEHP溶出的主要因素,并且随着苯甲醇浓度升高和滴注时间的延长,DEHP的溶出量相应增加。结论:苯甲醇促进了一次性输液器中DEHP的溶出,溶出量与苯甲醇浓度和滴注时间呈正相关。     

HPLC法测定PVC输液器中TOTM在脂肪乳注射液中的溶出量

目的：建立了高效液相色谱法测定聚氯乙烯（PVC）输液器中偏苯三酸三辛酯（TOTM）在脂肪乳注射液中的溶出量。方法使用 C18（4．6×100mm,3．5μm）色谱柱,以水∶乙腈为流动相,梯度洗脱,检测波长270nm。结果 TOTM 在0．3525～14．10μg? mL －1浓度范围类线性关系良好（r＝0．9999）,平均回收率为95．13％～102．1％,相对标准偏差为3．0％～4．3％。3批 PVC输液器的检测结果显示：在25℃和40℃模拟临床使用条件下,脂肪乳注射液中TOTM的溶出量分别在1．105～1．519mg和1．586～2．017mg之间,均小于成人的耐受摄入量（7mg）。结论该方法简单、准确,可用于PVC输液器中TOTM在脂肪乳注射液中的溶出量的测定。     

高效液相色谱法测定塑料输液容器中四种常用抗氧剂的含量

目的：建立塑料输液容器中四种常用抗氧剂含量测定方法.方法：采用Dikma Diamonsil C18色谱柱（4.60 mm×250 mm,5 μm）,流动相为乙腈-四氢呋喃-水（60∶30∶10）,柱温30 ℃,检测波长275 nm.结果：四种抗氧剂在0～0.2 mg·mL-1范围内均呈良好的线性关系（r=0.999）,抗氧剂1010回收率为97.2%（RSD=3.7%）,抗氧剂1330回收率为95.4%（RSD=3.6%）,抗氧剂1076回收率为94.8%（RSD=3.8%）,抗氧剂168回收率为95.2%（RSD=4.4%）.结论：该方法准确、灵敏、简便,适用于测定塑料输液容器中四种常用抗氧剂的含量.     

Disposition of orally administered di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate in the rat

The dispositon of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) was studied in the rat. Three hours after a single oral dose of DEHP (2.8 g/kg), plasma concentrations of 8.8±1.7 g/ml DEHP and 63.2±8.7 g/ml MEHP were reached. MEHP levels declined with a half-life of 5.2±0.5 h. The ratio of the area under the plasma concentration-time curve of MEHP to that of DEHP was 16.1±6.1. When ¹⁴CDEHP was administered, 19.3±3.3% of the radioactivity was excreted in the urine within 72 h, the rest being excreted in the faeces. The urinary excretion rate of total radioactivity declined with a half-life of 7.9±0.5 h. Single administration of MEHP (0.4 g/kg) resulted in plasma concentrations of 84.1±14.9 g/ml 3 h after dosing; the half-life of MEHP was 5.5±1.1 h. Multiple dosing with DEHP (2.8 g/kg/day) for 7 consecutive days produced no accumulation of DEHP or MEHP in plasma.     

输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的测定

目的 建立输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的高效液相色谱测定法。方法 采用Diamosil-C₁₈(4.6 mm×250 mm,5 μm)色谱柱;流动相为甲醇-水(80∶20),检测波长为227 nm,流速1.0 mL·min^-1。结果 双酚A在1.354~27.08 ng内呈良好的线性关系(r=0.999 9);聚碳酸酯组合盖中双酚A含量和双酚A向输液中迁移量测定的平均回收率分别为91.7%(RSD=2.3%)和93.9%(RSD=1.8%)。结论 该方法准确、灵敏、简便,适用于对输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的测定。     

Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats

Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely present in the environment and some products with phthalate plasticizer. It has become a serious problem in recent years. The effect of DEHP on female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on hypothalamus-pituitary-ovarian axis in adult female rats. Compared with control rats, the DEHP-treated rats showed: (1) lower body weight; (2) lower organ coefficient of ovary; (3) higher GnRH level in the hypothalamus; (4) higher mRNA and protein levels of GnRHR in the pituitary; and (5) lower serum sex hormone levels. Our data reveal that DEHP exposure may lead to the disruption of estrogen biosynthesis pathways in female rats and imbalance of hypothalamus-pituitary-ovarian axis. DEHP may impose negative influence on the development and function of the reproductive system in female rats.     

Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells

Tamoxifen, an estrogen receptor antagonist, has been clinically used as an antitumor drug and induces apoptosis in GH3 pituitary cells. Although di-(2-ethylhexyl) phthalate (DEHP) is a well-known environmental estrogen and the exposure to this chemical is well expected, reports are limited regarding effects of DEHP on tamoxifen-induced apoptosis in pituitary cells. In the cytotoxicity assay, the reduced cell viability in tamoxifen-treated GH3 cells was reversed by DEHP (250 μM) treatment for 4 days. To characterize cell death, cells were stained using Hoechst 33258. Apoptotic morphological change such as chromatin condensation induced by tamoxifen was suppressed by treatment with DEHP. Flow cytometric analysis revealed that the number of apoptotic cells induced by tamoxifen was significantly decreased by DEHP treatment. Enhanced poly (ADP-ribose) polymerase (PARP) cleavage by tamoxifen treatment was also inhibited by DEHP. These results suggest that DEHP suppresses tamoxifen-induced apoptosis in association with its estrogenic effect in GH3 cells and might counteract the therapeutic effect of tamoxifen.     

Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice

Di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate (MEHP) were administered PO or IP to pregnant ICR mice at varying doses on days 7, 8, and 9 of gestation. In groups given DEHP orally, resorptions and malformed fetuses increased significantly at 1,000 mg/kg. Fetal weights were also significantly suppressed. Anterior neural tube defects (anencephaly and exencephaly) were the malformations most commonly produced. No teratogenic effects were revealed by IP doses of DEHP and PO or IP doses of MEHP, although high doses were abortifacient and lethal to pregnant females. Thus DEHP is highly embryotoxic and teratogenic in mice when given PO but not IP. The difference in metabolism, disposition, or excretion by the route of administration may be responsible for the difference in DEHP teratogenicity. Although MEHP is a principal metabolite of DEHP and is several times more toxic than DEHP to adult mice, it seems that MEHP and its metabolites are not teratogenic in ICR mice.     

The occurrence of phthalic acid esters in various samples of commercially available sodium chloride injections (Indian Pharmacopoeia)

Conclusive evidence for the presence of di(2-ethylhexyl) phthalate (DEHP) in 15 out of 17 commercially available sodium chloride injection (Indian Pharmacopoeia) samples was obtained and concentration levels as high as 11.0 mg/500 ml of saline were detected. The presence of such contaminants in i.v. fluids, avoidable by the institution of appropriate quality control measures before manufacturing and marketing, is a matter of serious concern. Stipulated specifications in different pharmacopoeias are meant only to ensure sterility and pyrogenicity, and it is advisable that cognisance be taken of the presence of toxic contaminants e.g. di(2-ethylhexyl) phthalate.