GC-MS/MS法测定苯甲酸阿格列汀中基因毒杂质2-氰基氯苄和邻二溴甲基苯腈的含量

目的:建立气相色谱-串联质谱法(GC-MS/MS)同时测定苯甲酸阿格列汀中基因毒杂质邻二溴甲基苯腈和2-氰基氯苄的含量.方法:采用6％氰丙基苯-94％二甲基硅氧烷(Agilent DB-624,30 m×0.32 mm,1.8μm)色谱柱,程序升温;进样口温度:260℃,进样体积1μL,线速度,5:1分流比进样.质谱条...     

2-(2-芳基)乙基苯甲酸的合成

以邻氰基氯苄为原料,与苯甲醛或2-噻吩甲醛经Wittig-Horner反应、水解及氢化反应制得2-(2-苯乙基)苯甲酸或2-(2-噻吩基)乙基苯甲酸,总收率分别约64%和60%。     

苯甲酸阿格列汀合成工艺的改进

目的改进苯甲酸阿格列汀的合成工艺。方法以6-氯尿嘧啶为起始原料,先与碘甲烷反应合成3-甲基-6-氯尿嘧啶,继而在无机碱的参与下与2-溴甲基苄腈反应得2-(6-氯-3甲基-2,4-二氯代-3,4-二氢-2H-嘧啶-1-基甲基)-苄腈,然后再在无机碱的存在下与(R)-3-氨基哌啶二盐酸发生取代反应,最后与苯甲酸成盐得苯甲酸阿格列汀。结果合成得到苯甲酸阿格列汀,总收率达到57.09%,纯度为99.6%。结论该工艺经过改进,降低了毒害,成本降低,经济环保,适合工业化生产。     

HPLC法测定苯甲酸阿格列汀的有关物质含量

目的建立高效液相色潽法测定苯甲酸阿格列汀有关物质含量的方法。方法采用Diamonsil C18色谱柱(250 mm×4.6 mm,5μm);乙腈为流动相A,体积分数为0.05%的三氟乙酸为流动相B,流速为1.0 m L·min-1,梯度洗脱;检测波长为278 nm;进样量为20μL;柱温为30℃。结果苯甲酸阿格列汀与有关物质A~G及未知杂质均能良好分离;各有关物质的质量浓度在0.1~2.0 mg·L-1内线性关系良好,r≥0.994(n=8);回收率为96.4%~104.3%(RSD≤1.7,n=9)。经对三批样品测定,有关物质的含量质量分数均低于限度(0.1%)。结论作者建立的方法简便准确、专属性强且灵敏度高,可作为苯甲酸阿格列汀有关物质的测定方法。     

苯甲酸阿格列汀的异构体控制方法

目的：探讨苯甲酸阿格列汀光学纯度与（R）-3-氨基哌啶双盐酸盐光学纯度之间的关系。方法：通过纯度测定方法检测（R）-3-氨基哌啶双盐酸盐的光学纯度,评价苯甲酸阿格列汀的光学纯度。结果与结论：（R）-3-氨基哌啶双盐酸盐光学纯度与苯甲酸阿格列汀之间的光学纯度有对应关系,通过控制（R）-3-氨基哌啶双盐酸盐光学纯度大于98%即可保证苯甲酸阿格列汀光学纯度合格。     

高效液相色谱法测定药用辅料苯甲醇中苯甲酸和苯甲醛含量

目的建立HPLC法同时测定药用辅料苯甲醇中苯甲酸和苯甲醛的含量。方法采用Acclaim 120 C18柱(4.6 mm×250 mm,5μm),流动相为乙腈-0.02%甲酸(用氨水调至p H=4.5)(30:70),流速为1.0 m L·min-1,检测波长为230 nm,柱温为35℃,进样量为20μL。结果苯甲酸在0.500 6¹5.02μg·m L-1内与峰面积线性关系良好,平均回收率均>100%,RSD均<1.3%(n=3);苯甲醛在0.505 215.02μg·m L-1内与峰面积线性关系良好,平均回收率均>100%,RSD均<1.3%(n=3);苯甲醛在0.505 2¹5.16μg·m L-1内与峰面积的线性关系良好,平均回收率均>108%,RSD均<0.15%(n=3)。结论本方法准确度高、重现性好,可用于苯甲醇中苯甲酸和苯甲醛的含量测定。     

HPLC法检查苯甲酸阿格列汀原料药的有关物质

目的:建立检查苯甲酸阿格列汀原料药中有关物质的方法。方法:采用高效液相色谱梯度洗脱法。色谱柱为C18,流动相A为0.2%磷酸溶液(pH 3.0),流动相B为乙腈,以1.0 ml/min流速进行梯度洗脱,检测波长为225 nm,进样量为20μl。采用不加校正因子主成分自身对照法检查特定杂质F-1的量。结果:苯甲酸阿格列汀与F-1及其他未知杂质均分离良好,前二者检查质量浓度线性范围分别为0.187 2⁰.748 8、0.184 50.748 8、0.184 5⁰.738 0μg/ml(r=0.999 7、0.999 9);F-1的检测限和定量限分别为2.5、7.5 ng,平均回收率为100.9%(RSD=1.10%,n=3);3批样品中F-1量均≤0.06%。结论:建立的方法灵敏快速、结果准确可靠,可作为苯甲酸阿格列汀原料药的有关物质检查方法。     

维格列汀原料药有关物质测定方法的研究

目的建立高效液相色谱法测定维格列汀原料药的有关物质。方法采用Waters XTerra MS C_(18)柱(4.6mm×50mm,3.5μm),以磷酸盐缓冲液-水-乙腈-甲醇(80:120:3:3)为流动相A,以磷酸盐缓冲液-乙腈-甲醇(8:9:3)为流动相B,梯度洗脱,检测波长为210nm;流速1.5m L/min。结果维格列汀与相邻杂质峰以及各杂质峰之间的分离度均大于1.3,检测限为1.2~1.6ng,定量限为2.4~3.3ng。结论该方法适用于维格列汀关物质的测定。     

HPLC法快速检测苦参素注射液中8个抑菌剂及苯甲醛

目的:建立快速筛查和同时测定苦参素注射液中8个抑菌剂(苯甲醇、苯酚、苯甲酸、山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)及苯甲醇降解产物—苯甲醛含量的高效液相色谱法。方法:应用Welch Materials XB-C18色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-0.02 mol.L-1醋酸铵溶液(冰醋酸调pH至5.0)梯度洗脱,流速1.0 mL.min-1,检测波长为211 nm(苯甲醇、苯酚),225 nm(苯甲酸),248 nm(苯甲醛),256 nm(山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)。结果:9个成分的峰面积与浓度的线性关系良好(r﹥0.9998),加样回收率为95.6%～102.2%。结论:本方法灵敏,快捷,准确,重复性好,可用于注射剂中抑菌剂的快速筛查与含量分析。     

HPLC法同时测定地西泮直肠凝胶中地西泮、 苯甲酸、苯甲醇含量

目的:建立了同时测定地西泮直肠凝胶中地西泮、苯甲酸、苯甲醇含量的高效液相色谱方法。方法:色谱柱为Agilent Eclipse Plus C18(4.6 mm×150 mm,3.5μm),以甲醇-0.05 mol·L^-1乙酸铵缓冲溶液(pH 4.0)为流动相,梯度洗脱,流速1.0 mL·min^-1,检测波长254 nm,柱温30℃,进样量10μL。结果:地西泮、苯甲酸、苯甲醇分离度均大于1.5,地西泮在0.010~0.200 mg·mL^-1范围内线性关系良好(r≥0.9999);苯甲酸在0.030~0.600 mg·mL^-1范围内线性关系良好(r≥0.9999);苯甲醇在0.0718~1.436 mg·mL^-1范围内线性关系良好(r≥0.9999);且地西泮、苯甲酸、苯甲醇的平均回收率均在98%~101%,RSD均小于2.0%(n=9)。结论:本法简单准确可靠,可用于地西泮直肠凝胶中地西泮、苯甲酸、苯甲醇的含量测定。     

Micellar liquid chromatographic analysis of benzyl alcohol and benzaldehyde in injectable formulations

An accurate, sensitive and selective reversed-phase micellar liquid chromatographic method was developed for simultaneous determination of benzyl alcohol and benzaldehyde. This method was applied in different injectable formulations containing diclofenac, piroxicam, lincomycin and clindamycin. The method showed excellent linearity in the range of 10-100 microg mL(-1) and 1-20 microg mL(-1) with the limit of detection (S/N = 3) 0.25 microg mL(-1) (2.3 x 10(-6) mol L(-1)) and 0.12 microg mL(-1) (1.13 x 10(-6) mol L(-1)) for benzyl alcohol and benzaldehyde, respectively. The suggested method was successfully applied to the analysis of the studied drugs in bulk with average recoveries of 100.1 +/- 1.0% for benzyl alcohol and 100.4 +/- 1.6% for benzaldehyde, and to the determination of benzyl alcohol and benzaldehyde in injectable formulations with the respective average recoveries of 99.8 +/- 0.3 and 100.0 +/- 0.4%.     

HPLC法快速检测苦参素注射液中8种抑菌剂及苯甲醛

目的:建立快速筛查和同时测定苦参素注射剂中8种抑菌剂(苯甲醇、苯酚、苯甲酸、山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)及苯甲醇降解产物———苯甲醛含量的高效液相色谱法。方法:应用WelchMaterials XB-C18色谱柱(4.6 mm×250 mm,5μm);流动相为乙腈-0.02 mol.L-1醋酸铵(冰醋酸调pH至5.0)梯度洗脱,流速1.0 mL.min-1,检测波长为211 nm(苯甲醇、苯酚),225 nm(苯甲酸),248 nm(苯甲醛),256 nm(山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)。结果:9种成分的峰面积与浓度的线性关系良好(r>0.9998),加样回收率为95.6%～102.2%。结论:本方法灵敏,快捷,准确,重复性好,可用于注射剂中抑菌剂的快速筛查与含量分析。     

Polarographic determination of benzaldehyde in benzyl alcohol and sodium diclofenac injection formulations

A rapid and sensitive polarographic method was developed for qualitative as well as quantitative analysis of the neurotoxic contaminant benzaldehyde in Na-diclofenac injections and in benzyl alcohol used for parental formulations. A well-defined differential pulse (DP) polarographic peak or a sampled direct current (SDC) wave was obtained at -1.39 V (vs. silver-silver chloride reference electrode) in Britton-Robinson buffer (pH 9.15) and at -1.41 V in 0.1 M LiCl solution. The reduction step involves a two-electron process, corresponding to the formation of benzyl alcohol. No peaks were observed in the anodic branch of the cyclic voltammogram, emphasizing the occurrence of an irreversible process. The peak current versus concentration relationship was found to be linear up to 50 microg/ml with the detection limit of 10 ng/ml and quantitation limit of 30 ng/ml. The relative standard deviations (S.D.) obtained for concentration levels of benzaldehyde as low as 25 microg/ml with the SDC and DP methods were 1.5 and 0.78% (n=10), respectively. Benzyl alcohol and Na-diclofenac are not electrochemically active, and metabisulfite reductions at -0.664 and -1.240 V do not interfere with the benzaldehyde reduction peak. The proposed methods (DP and SDC polarography) have been applied satisfactorily to the determination of benzaldehyde traces in benzyl alcohol and in different pharmaceutical products such as Na-diclofenac injectable formulations.     

Squamocin and benzyl benzoate, acaricidal components of Uvaria pauci-ovulata bark extracts

Annonaceae have been commonly described in traditional medicine as remedies against head lice and for their insecticidal properties. Acaricidal effects of Uvaria pauci-ovulata bark extracts were investigated on Dermatophagoides pteronyssinus, the European house dust mite, and compared with those of benzyl benzoate used as standard acaricidal compound. A dichloromethane extract was the most effective with an EC50 = 0.028 g/m2 after a 24 h period as compared with benzyl benzoate (EC50 = 0.06 g/m2). Bioassay-guided fractionation of this extract led to the isolation of benzyl benzoate and squamocin; this latter compound also had acaricidal properties (EC50 = 0.6 g/m2). Moreover, squamocin was shown to potentiate the activity of benzyl benzoate using the fractional effective concentration (FEC) method.     

High-performance liquid chromatographic method for the simultaneous determination of 24 fragrance allergens to study scented products

The European legislation on cosmetic products has recently required the declaration of 26 compounds (24 volatile chemicals and 2 natural extracts) on the label of final products when exceeding a stipulated cut-off level. In this work a rapid reliable and specific RP-HPLC method coupled with diode array detector (DAD) has been developed for the simultaneous determination and quantification of the 24 volatile chemicals: amyl cinnamal, benzyl alcohol, cinnamyl alcohol, citral, eugenol, hydroxy-citronellal, isoeugenol, amylcinnamyl alcohol, benzyl salicylate, cinnamal, coumarin, geraniol, Lyral (hydroxy-methylpentylcyclohexene carboxaldehyde), anisyl alcohol, benzyl cinnamate, farnesol, Lilial (2-(4-tert-butylbenzyl)propionaldehyde) linalool, benzyl benzoate, citronellol, hexyl cinnamal, limonene, methylheptin carbonate, alpha-isomethyl ionone (3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one). The 24 analytes were appropriately separated over a running time of 40 min, on a C18 column using a simple gradient elution (acetonitrile/water) with flow rate from 0.7 to 1.0 ml/min and UV acquisition at 210, 254 and 280 nm. All calibration curves showed good linearity (r2>0.99) within test ranges. The method was successfully applied to the qualitative and quantitative determination of the potential allergens in four commercial scented products, with satisfactory accuracy and precision. The results indicated that this simple and efficient method can be used for quality assessment of complex matrices such us cosmetic scented products.     

Stability-indicating liquid chromatographic determination of etoposide and benzyl alcohol in injectable formulations

Simple and specific assays for etoposide, related impurities, and benzyl alcohol, as well as its degradation product, benzaldehyde, in injectable formulations were developed using high-performance liquid chromatography (HPLC). Etoposide, benzyl alcohol, benzaldehyde, and four etoposide impurities were determined with a mobile phase containing 26% acetonitrile in pH 4.0 acetate buffer with methyl p-aminobenzoate as the internal standard. Two etoposide precursors were additionally determined using 60% acetonitrile in the mobile phase with biphenyl as the internal standard. The assays were run sequentially. The etoposide assay had a total variability of less than 1% (RSD) and a recovery from placebo of 99.4%. Mean recovery of impurity standards spiked at the 2% level relative to the etoposide level was 98%. Recoveries for benzyl alcohol and benzaldehyde were 100.5% and 102.2%, respectively. Absorbance ratios generated from samples and compared with undegraded standards demonstrated specificity for etoposide. Similar response regression equations with correlation coefficients greater than 0.99 were obtained for etoposide and four impurities over the 2-8 micrograms/mL concentration range, indicating that an etoposide standard could be used to quantitate low impurity levels down to 0.2% relative to the etoposide injectable concentration. Benzaldehyde could be reliably detected at concentrations down to 0.5 micrograms/mL, equivalent to 0.16% of the benzyl alcohol level.