气相色谱法测定依托咪酯注射液中丙二醇的含量

目的：建立依托咪酯注射液中辅料1,2-丙二醇含量测定方法。方法：采用气相色谱法,以正辛醇为内标,色谱柱为INNOWAX毛细管柱（30m×0．53min×1μm）,汽化室温度220℃,程序升温：初始温度为120℃,保持3min;以每分钟10℃的速度升至250℃,保持5min。载气：氮气,流速为4mL·min^-1;检测室FID温度250℃,尾吹30mL·min^-1,进样量1μL。结果：上述测定方法能使内标（正辛醇）、1,2-丙二醇、1,3-丙二醇和二甘醇良好分离,1,2-丙二醇在50-1500μg·mL^-1的范围内丙二醇浓度（C）与峰面积响应值（f=A／A内）有良好的线性关系,r=0．9999;进样精密度、日内测定精密度、日间精密度的RSD分别为1．5％、1．5％、1．3％;平均回收率（n=9）为100．6％,RSD为1．4％：方法定量限和检测限分别为2．0、0．62μg·mL^-1。结论：气相色谱法可以用于控制依托咪酯注射液中辅料1,2-丙二醇的含量。     

固相萃取-气相色谱-质谱法测定二羟丙茶碱中痕量3-氯-1,2-丙二醇

目的:建立二羟丙茶碱中痕量3-氯-1,2-丙二醇(3-MCPD)的气相色谱-质谱联用定性定量方法。方法:试样经饱和氯化钠提取,弗罗里硅土层析柱分离净化,旋转蒸发浓缩,三氟乙酸酐衍生后,进行气相色谱-质谱联用(SIM模式)检测。结果:3-氯-1,2-丙二醇在10～500μg·kg-1范围呈良好线性关系(r=0.9993,n=5),检出限为2.3μg·kg-1,三水平加标回收率均在96%以上,RSD在0.249%～1.151%之间。结论:该方法灵敏度高,重现性好,适用于药品中痕量3-氯-1,2-丙二醇的测定。     

毛细管柱气相色谱法测定注射液中丙二醇的含量

目的：建立气相色谱法测定注射液中的丙二醇。方法：采用毛细管柱气相色谱法,FID检测器,色谱柱为HP-INNOWax毛细管柱（30mx0.32mmx0.25μm）,载气为氮气,运用程序升温的方法测定注射液中丙二醇的含量。结果：得到线性回归方程为Y=0.000859X＋0.009051,相关系数r=0.9992,平均回收率为99.7%（n=9）。结论：方法操作简便、快速,能满足检测注射液中丙二醇含量的要求。     

LLE-GC-MS法同时测定甘磷酸胆碱中的缩水甘油和3-氯-1,2-丙二醇

目的 建立液液萃取-气相色谱-质谱法(LLE-GC-MS)同时测定甘磷酸胆碱原料药中的基因毒性杂质缩水甘油和3-氯-1,2-丙二醇。方法 采用酸性氯化钠溶液和酸性无水硫酸钠溶液分别处理甘磷酸胆碱原料药，经硅藻土柱净化、富集后用七氟丁酰基咪唑衍生，采用气相色谱-质谱法(SIM模式)进行检测，以D₅-3-氯-1,2丙二醇作为内标，通过双样本差减法计算样品中缩水甘油和3-氯-1,2-丙二醇的含量。结果 2种基因毒性杂质与内标物的峰面积比值在0.1～2 mg·L^-1浓度范围内呈线性相关，相关系数(r)均不小于0.999 2,样品的加样回收率为86.4%～103.3%(RSD<6.0%,n=9)。结论 该方法灵敏度高、专属性强，适用于甘磷酸胆碱原料药中缩水甘油和3-氯-1,2-丙二醇的测定。     

GC—MS法应用于丙二醇的质量控制及二甘醇检查

目的：建立丙二醇的质量控制和二甘醇检查的方法。方法：应用气相色谱-质谱联用仪（GC—MS）对丙二醇和二甘醇同时进行分析；色谱柱起始温度40℃，维持时间5min，以20℃&#183;min^-1速率升至80℃，维持1min．再以30℃&#183;min^-1升至250℃，维持5min，不分流进样，通过监测总离子流色谱图以及色谱峰的质谱图，对丙二醇、杂质以及二甘醇进行检测。结果：该方法对丙二醇和二甘醇都具有良好的专属性、灵敏度和精密度。结论：该方法能用于丙二醇的质量控制和其中的二甘醇的检查。     

毛细管气相色谱法测定羟丙基-β-环糊精中的有机溶剂残留量

目的：建立毛细管气相色谱法测定羟丙基-β-环糊精中乙醇和1,2-丙二醇的残留量的方法。方法：色谱柱为DB-624石英毛细管柱,柱温采用程序升温,FID检测器,检测器温度为250℃,进样口温度为250℃,以二甲亚砜为溶剂。结果：乙醇、1,2-丙二醇的检测浓度的线性范围分别为0．1～5．0mg·ml^-1（r=0．9999）、0．1～5．0mg·ml^-1（r=0．9997）;平均回收率为分别为99．0％,98．2％,（RSD分别为1．9％,2．2％）;最低检出限分别为1．03,0．81ng;3批样品中2种有机溶剂残留量均符合《中国药典》要求。结论：本方法简单、准确、灵敏度高、重复性好,可用于该药物中有机溶剂残留量的测定。     

气相色谱法分离测定环孢素A中乙醇及丙二醇的含量

建立一个气相色谱条件同时分离测定环孢素Ａ中乙醇及丙二醇的含量。方法：以ＧＤＸ－１０１为固定相,柱长为２ｍ,进样品温度为２１０℃,检测器为２８０℃,柱温采用程序升温,氮气为载气,以二甲基亚砜为溶剂,以正丙醇为内标。结论此气相色谱条件可同时测定环孢Ａ中乙醇及丙二醇的含量测定方法简便准确。     

GC-MS法对药用辅料1,2-丙二醇未知杂质的定性研究

目的：对1,2-丙二醇样品中未知杂质进行质谱确证。方法：运用GC-MS法,采用AB-INOWAX毛细管柱（30 m×0.25 mm,0.25μm）;柱温：起始温度60℃,保持3 min,以10℃·min-1升温至220℃,保持4 min;EI源温度：230℃。结果：样品中未知杂质实为已知杂质一缩二丙二醇的异构体。结论：该方法简便、快速、灵敏度高,可用于1,2-丙二醇中有关物质的定性检测。     

气相色谱法测定维生素K1注射剂中1，2-丙二醇的含量

目的建立GC法测定维生素K1注射剂中1,2-丙二醇的含量。方法采用Agilent DB—WAX气相毛细管柱（0．32mm×30m,0．25μm）,FID检测器,程序升温：80℃维持1min,再以10℃·min^-1升温至230℃维持4min,进样口温度：230℃,检测器温度：250℃。结果维生素K1注射剂中1,2．丙二醇在0．1025～4．0998nag·mL^-1与峰面积呈良好线性关系（r=0．9999）,平均回收率为97．5％,RSD为0．40％（n=9）。结论本方法准确度高、重现性好,可用于维生素K1注射剂中1,2-丙二醇含量的测定。     

气相色谱法检查依托咪酯注射液中二甘醇的含量

目的建立依托咪酯注射液中二甘醇检查方法。方法采用气相色谱法,以丙三醇为内标,色谱柱为INNOWAX毛细管柱（30m×0.53mm×1μm）,汽化室温度220℃,程序升温：初始温度为120℃,保持3分钟;以每分钟10℃的速度升至230℃,保持5min。载气：氮气,4mL·min^-1;检测室温度250℃,尾吹30mL·min^-1,进样量1μL。结果上述测定方法能使内标（丙三醇）、1,2-丙二醇、1,3-丙二醇和二甘醇良好分离,在11μg·mL^-1-167μg·mL^-1的范围内浓度（C）与峰面积响应值（f=A/A内）有良好的线性关系,r=0.9995;进样精密度、日内测定精密度、日间测定精密度的RSD%分别为1.1%、0.9%和1.0%;平均回收率（n=9）为100.9%,RSD为1.5%;方法定量限和检测限分别为0.56μg·mL^-1,0.17μg·mL^-1。结论气相色谱法可以用于检查控制依托咪酯注射液中二甘醇的含量。     

Is propylene glycol an inert substance?

The effect of 30 day administration of undiluted propylene glycol (1,2-propanediol, PG) on plasma and liver lipids was studied in adult male SpragueD?awley rats. When compared with the control group no significant difference was observed in plasma concentration of total phospholipids, cholesterol, triglycerides and free fatty acids, and in liver concentration of phospholipids, triglycerides and gangliosides. Liver total cholesterol was moderately, but significantly, increased.     

Developmental pharmacokinetics of propylene glycol in preterm and term neonates

AIM

Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg PG/200 mg phenobarbital) in preterm and term neonates.

METHODS

A population pharmacokinetic analysis was performed based on 372 PG plasma concentrations from 62 (pre)term neonates (birth weight (bBW) 630–3980 g, postnatal age (PNA) 1–30 days) using NONMEM 6.2. The model was subsequently used to simulate PG exposure upon administration of paracetamol or phenobarbital in neonates (gestational age 24–40 weeks).

RESULTS

In a one compartment model, birth weight and PNA were both identified as covariates for PG clearance using an allometric function (CL_i= 0.0849 × {(bBW/2720)^1.69× (PNA/3)^0.201}). Volume of distribution scaled allometrically with current bodyweight (V_i= 0.967 × {(BW/2720)^1.45}) and was estimated 1.77 times higher when co-administered with phenobarbital compared with paracetamol. By introducing these covariates a large part of the interindividual variability on clearance (65%) as well as on volume of distribution (53%) was explained. The final model shows that for commonly used dosing regimens, the population mean PG peak and trough concentrations range between 33–144 and 28–218 mg l⁻¹ (peak) and 19–109 and 6–112 mg l⁻¹ (trough) for paracetamol and phenobarbital formulations, respectively, depending on birth weight and age of the neonates.

CONCLUSION

A pharmacokinetic model was developed for PG co-administered with paracetamol or phenobarbital in neonates. As such, large variability in PG exposure may be expected in neonates which is dependent on birth weight and PNA.     

Pharmacokinetics of propylene glycol in the rabbit

Propylene glycol (PG) is widely used as a drug solvent in the pharmaceutical industry. However, it has produced central nervous system toxicity during chronic administration. The current study was undertaken to describe the pharmacokinetics of propylene glycol during acute and constant-rate intravenous dosing, using the rabbit as an animal model. In the acute dosing experiment, metabolism of PG was the dominant disposition pathway, characterized by concentration-dependent metabolic clearance. Renal excretion of PG accounted for only 2.4 to 14.2% of the total dose following acute administration due to significant reabsorption in the rabbit kidney. An ascending-convex relationship exists between renal clearance and urine flow. During constant-rate intravenous infusion studies, there was a disproportionate relationship between infusion rate and steady-state concentration, providing further evidence for capacity-limited disposition kinetics. The ascending-convex relationship between renal clearance and urine flow was also apparent in the long-term infusion studies.     

Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro.

The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA.     

藻酸双酯钠及其分级产物免疫调节作用比较研究

目的探讨海洋药物藻酸双酯钠(PSS)的免疫调节作用及其构效关系。方法采用体外免疫细胞培养法检测PSS及其分级产物的免疫调节作用,根据分级产物结构差异,探讨PSS分级产物的免疫活性构效关系。结果PSS能够促进脾脏淋巴细胞的增殖,提高巨噬细胞吞噬功能,同时能抑制刀豆蛋白A(ConA)及脂多糖(LPS)促进的免疫细胞的增殖作用。结论PSS具有显著的免疫调节作用,不同的糖链长度对免疫细胞作用不同。     

GC毛细管柱内标法测定环孢素软胶囊中乙醇与丙二醇的含量

目的采用市售GC毛细管柱替代进口注册标准中的玻璃填充柱,以正丙醇为内标、二甲基亚砜为溶剂测定环孢素软胶囊中的乙醇和丙二醇含量。方法采用正丙醇为内标,聚二甲基硅氧烷为固定相的毛细管柱(CP-SIL-5,50 m×0.53 mm,2.0μm);柱温程序升温,检测器温度(FID):250℃;载气:氮气;分流比:10∶1;进样口温度:230℃;进样量:0.2μL。结果乙醇和丙二醇质量浓度在1.5~3.5mg·mL-1范围内呈良好的线性关系,r=0.997 5~0.998 1。高、中、低3种体积分数乙醇的平均回收率为100.8%(RSD=0.9%);丙二醇的平均回收率为101.0%(RSD=0.8%)。结论该方法操作简便,能够准确测定乙醇和丙二醇的含量。     

甘糖酯抗氧化作用的分子机制

目的探讨甘糖酯(PGMS)清除自由基抗氧化作用的分子机制。方法给大鼠ig高脂乳剂建立高脂血症模型,分成对照组、甘糖酯治疗组、甘糖酯+DDC组,治疗3周。检测血清、肝脏、脾脏和主动脉中丙二醛(MDA)的含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性,以及Cu,Zn-SOD mRNA的表达水平。结果甘糖酯治疗组大鼠,丙二醛(MDA)含量降低,SOD,GSH-Px和CAT的活性显著升高,Cu,Zn-SOD mRNA的表达水平增加;而甘糖酯和DDC联合用药治疗组,DDC抑制了甘糖酯诱导的Cu,Zn-SOD mRNA表达水平和SOD活性的升高,造成MDA含量的相应升高。结论甘糖酯通过诱导抗氧化酶SOD,GSH-Px和CAT的活性,增加Cu,Zn-SOD mRNA的表达水平,清除体内过多的氧自由基,达到抗氧化的目的。     

甘糖酯对高脂血症大鼠主动脉中MCP-1表达的抑制作用甘糖酯对高脂血症大鼠主动脉中MCP-1表达的抑制作用

目的探讨甘糖酯对高脂血症大鼠主动脉中单核细胞趋化蛋白-1(MCP-1)表达的影响。方法以甘糖酯或甘糖酯辅以超氧化物歧化酶(SOD)抑制剂diethyldithiocarbamate(DDC)治疗高脂血症大鼠3周,测定SOD活性、脂质过氧化产物丙二醛(MDA)的浓度变化及主动脉中MCP-1 mRNA的表达。结果甘糖酯治疗后MCP-1 mRNA的表达量显著降低,呈剂量依赖性关系;并升高SOD活性、降低MDA的含量;而在DDC作用下SOD活性被抑制,使MDA含量又升高,但是MCP-1 mRNA水平不受影响,仍处于降低状态。结论甘糖酯抑制高脂血症大鼠主动脉中MCP-1 mRNA的表达,且此抑制作用与其降低MDA的作用无关。     

Effect of propylene glycol,Azone and n-decylmethyl sulphoxide on skin permeation kinetics of 5-fluorouracil

The effect of propylene glycol (PG), azone (LDA) and n-decylmethyl sulfoxide (LDB) on the permeation course of fluorouracil through the hairless mouse skin was studied. Steady-state fluxes and permeability coefficients were measured in buffer solutions and in systems containing the enhancing agents. The permeation rates of fluorouracil have been shown to be highly pH dependent in the pH range of 5–9, the rate decreases with an increase in pH. The solubility of fluorouracil in pure propylene glycol at equilibrium measured by the solubility method was found to be 2.2 mg · ml^?1 at 25°C which is a relatively low value as compared to the solubility in water. The effect of various concentrations of propylene glycol in aqueous donor solutions on the drug permeation rate was examined at pH's 5.7 and 9.0. It was found that propylene glycol decreases the permeation flux when increasing concentrations are added to the aqueous pH 5.7 system; however, at pH 9, a strong enhancement effect was shown. PG was also found to decrease the drug reservoir in the hairless mouse skin e.g. 8.4 and 2.8 mg · (mg skin)^?1 for buffer pH 9 and PG/aqueous solution pH 9 systems, respectively. The concentration dependent enhancement effects of azone and n-decylmethyl sulfoxide have been measured. Both have been found to be potent enhancing agents. However, at relatively low concentrations such as 5%, Azone induced a 50-fold and n-decylmethyl sulfoxide only a two-fold enhancement of the drug steady-state flux. At high concentrations as much as 40%, n-decylmethyl sulfoxide appears to be more effective than Azone. The fluxes measured with these systems were 0.21, 0.17 and 0.003 mg · cm^?2 · h^?1 for the n-decylmethyl sulphoxide, Azone and PG/H₂O systems, respectively.     

甘糖酯降低实验性糖尿病大鼠肾脏ICAM-1,VCAM-1表达

目的探讨甘糖酯(PGMS)对糖尿病大鼠肾脏细胞间黏附分子-1(ICAM-1)、血管细胞间黏附分子-1(VCAM-1)表达的影响和保护作用.方法链尿佐菌素(STZ)诱发大鼠糖尿病.甘糖酯(52,26mg·kg-1·d-1)治疗8周,测定血糖、糖化血红蛋白、肾脏/体重,24h尿蛋白排泄率,利用免疫组织化学、逆转录聚合酶链式反应(RT-PCR)和蛋白印迹(Western Blot)技术检测肾脏组织ICAM-1,VCAM-1分布及表达.结果与糖尿病模型组比较,PGMS有减轻肾脏肥大趋势;降低尿蛋白排泄率(P＜0.05);免疫组化显示PGMS能明显减少ICAM-1,VCAM-1在肾脏组织的分布;RT-PCR,Western bbt结果显示PGMS能明显降低ICAM-1,VCAM-1 mRNA和蛋白水平表达,高剂量组效果优于低剂量组但无统计学差异.ICAM-1,VCAM-1表达与肾脏肥大、尿蛋白存在部分正相关.结论PGMS能降低STZ诱发的糖尿病大鼠肾脏ICAM-1,VCAM-1 mR-NA和蛋白水平.