离子色谱法测定食品添加剂三聚磷酸盐中的杂质含量

研究了离子色谱法检测食品添加剂三聚磷酸盐中杂质含量的分析方法。用NaOH梯度淋洗,流速为1.8 mL/min,成功地同时测定了三聚磷酸盐中的Cl- NO- 3 SO2- 4 磷酸盐 焦磷酸钠 三偏磷酸钠等杂质的含量。各杂质在检测条件下有很好的线性,所测杂质的相对标准偏差范围为0.22%-8.32%。采用AS11型阴离子色谱柱,样品测定的整个过程可在15 min内完成。实验结果表明,该方法具有分析时间短 线性范围宽 灵敏准确 试剂用量少等优点。     

Factorial Design in Optimization of Chromatographic Separation of Ramipril and Its Impurities

In this paper optimization of chromatographic retention of ramipril and its five impurities employing factorial design is presented. On the basis of preliminary experiments three factors were chosen as inputs (acetonitrile content, pH of the mobile phase and buffer concentration) and retention factor as output. As optimal full factorial design 2³ was chosen, factors were examined at two different levels “low” and “high”. Three replications at zero level were added in order to check linearity and complete statistical tests. Relationship between inputs and output is presented in form of second order interaction model. Adequacy of model was explained using analysis of variance. After analysis of results optimal chromatographic conditions were set. Separations were conducted on a C₁₈ column with a mixture of acetonitrile and water phase (TEA in potassium dihydrogen phosphate) in ratio 23:77 v/v. Finally, the LC method was validated and applied for quality control analysis of commercially available tablets. The proposed method is simpler and faster as compared to existing official methods and therefore more adequate for routine control of ramipril during shelf life. Also a general approach which includes factorial design in method optimization offers a possibility for predicting and following the chromatographic behavior of such complex mixtures.     

Development and Validation of Rapid Resolution RP-HPLC Method for Simultaneous Determination of Atorvastatin and Related Compounds by Use of Chemometrics

Abstract

A Rapid Resolution Reversed Phase High-Performance Liquid Chromatography (RR RP-HPLC) method has been developed and validated for the simultaneous determination of atorvastatin and seven related compounds specified as impurities. Experimental design was used during method optimization (full factorial 3² design) and robustness testing (central composite design). Chromatography was performed with mobile phase containing phosphate buffer pH 3.5 and a mixture of 10% (v/v) tetrahydrofuran in acetonitrile as organic modifier. A Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm × 50 mm, 1.8 µm particle size column was used. The developed method allowed determination of Atorvastatin Calcium (ATV Ca) purity and level of impurities in drug substances.     

Development and Validation of a LC Method for the Determination of Pramipexole Using an Experimental Design

A rapid and sensitive RP-HPLC method with UV detection for routine control of pramipexole in tablets was developed. Chromatography was performed with mobile phase containing a mixture of acetonitrile/phosphate buffer (60/40; v/v) with a flow rate of 0.8 mL min⁻¹. Quantitation was accomplished with the internal standard method; the procedure was validated by linearity (correlation coefficient = 0.99892), accuracy, robustness and intermediate precision. Limit of quantitation and limit of detection were found to be 4.5 μg and 1.4 μg respectively, which indicates the method is highly sensitive. Experimental design was used during validation to calculate method robustness and intermediate precision, for robustness test three factors were considered; percentage v/v of acetonitrile, flow rate and pH; an increase in the flow rate results in a decrease of concentration found of the drug, while the percentage of organic modifier and temperature have no important effect on the response. For intermediate precision measure the considered variables were: analyst, equipment, days and obtained RSD value (0.56%, n=24) which indicated a good precision of the analytical method. The method was found to be applicable for determination of the drug in tablet formulations and the results of the developed method were compared with those of the UV spectrophotometric method to access the active pramipexole content. Revised: 13 March and 25 April 2006     

Chromatographic Techniques for the Determination of Free Phenol in Foundry Resins

Phenol is a toxic compound present in a wide variety of foundry resins. Its quantification is important for the characterization of the resins as well as for the evaluation of free contaminants present in foundry wastes. Two chromatographic methods, liquid chromatography with ultraviolet detection (LC-UV) and gas chromatography with flame ionization detection (GC-FID), for the analysis of free phenol in several foundry resins, after a simple extraction procedure (30 min), were developed. Both chromatographic methods were suitable for the determination of phenol in the studied furanic and phenolic resins, showing good selectivity, accuracy (recovery 99–100%; relative deviations <5%), and precision (coefficients of variation <6%). The used ASTM reference method was only found to be useful in the analysis of phenolic resins, while the LC and GC methods were applicable for all the studied resins. The developed methods reduce the time of analysis from 3.5 hours to about 30 min and can readily be used in routine quality control laboratories.     

反相高效液相色谱法同时测定丁酸氯维地平中10种相关杂质

建立反相高效液相色谱辅-光电二极管阵列检测器(RP-HPLC)法同时测定丁酸氯维地平原料药中的10种杂质。色谱柱为Symmetry C18柱(250 mm×4.6 mm,5μm),流动相为0.05 mol/L Na H2PO4溶液(pH 2.5)-乙腈/甲醇(3∶2,V/V),梯度洗脱,柱温35℃,流速为1.5 m L/min,检测波长220 nm。丁酸氯维地平及其10个已知杂质能够达到良好的分离,且各组分在各自测定浓度范围内与峰面积的线性关系良好(r≥0.9970);丁酸氯维地平及杂质1~10的检出限(S/N=3)在0.15~0.90 mg/L之间。本方法快速、简便、有效,可用于丁酸氯维地平原料药的质量控制管理。     

Crossed D-Optimal Experimental Design Methodology for the Chromatographic Separation of Antihypertensive Drugs

An efficient, isocratic, reversed-phase high performance liquid chromatography method was developed, optimized, and validated to separate nine antihypertensive drugs by experimental design methodology and the Crossed D-Optimal process. In order to find the most suitable separation conditions, twenty-three experiments were carried out, based on the simultaneous effects of three solvent (methanol, acetonitrile, and water) compositions in combination with different pH values of the mobile phase. The components were cross-combined with a pH factor (quadratic x quadratic process), whereas optimal adjusted models were used for the eight individually chosen responses. The optimal mobile phase consisted of methanol, acetonitrile, and 0.05 M aqueous ammonium acetate at pH 3.1 (18:26: 56 v/v/v, pH adjustment with formic acid). Analysis was carried out on a C₁₈ column (150 × 4.6 mm, 5 µm) at 40 °C using photodiode array detection at 242 nm. The system was found to produce sharp and well resolved peaks for all analytes while the retention times ranged from 2.3 to 31 min. The method was linear (r² > 0.999) and reliable since the accuracy (recovery = 100 ± 2.9) and the precision (relative standard deviation < 2%) met International Conference on Harmonization guidelines. The technique was shown to be a useful tool for separating complex mixtures using experimental design methodology.     

Development of an HPLC Assay Methodology for a Desonide Cream with Chemometrics Assisted Optimization

A new reversed-phase liquid chromatographic method for the separation and simultaneous quantification of desonide, sorbic acid, methylparaben, propyl gallate, and the major degradation product of desonide in a hydrophilic cream was developed with the aid of experimental design, resolution loss functions, and chemometrics methods. A strategy involving a screening phase and a fractional factorial design revealed the most influent chromatographic variables (pH and organic solvent content). The arc tangent resolution function was adopted as the optimization loss function. These variables were further optimized using a central composite design. Multivariate curve resolution and partial least squares regression were tested to optimize the chromatographic run time. The latter revealed to be superior in terms of precision and allowed the validation of a method with a total run time 3 times lower (approximately 8 min). The experimental design and chemometrics models enabled an efficient use of time and resources in predicting the optimum separation conditions for the desonide formulation. The validation of the resulting method according to the current ICH guidelines confirmed its selectivity, linearity, accuracy, and precision.     

Determination of Tandospirone and its Impurities in Drug Formulations by LC-UV and LC-MS

This work describes the determination of tandospirone in bulk drug substance and formulated products by a reversed-phase liquid chromatographic method with UV detection. Chromatographic separation was performed on a C₁₈ column with a mobile phase of a binary mixture of methanol and water (70:30, v/v) delivered at a flow rate of 0.5 mL min^–1 and detection was performed at 243 nm. The proposed LC method is selective, precise and accurate for the determination of tandospirone in the presence of its manufacturing impurities with a limit of quantitation of 0.54 g mL^–1. A preliminary study for the identification of the major manufacturing impurities was made by liquid chromatography-mass spectrometry with electrospray ionization source operated in a positive ion mode.     

Determination of Nisoldipine and Its Impurities in Pharmaceuticals

A method has been established for separation of nisoldipine and impurities, for example reactants, products of side-reactions, and photodegradation products, by HPTLC on LiChrospher Si 60 F_254s plates with detection at 280 nm. The mobile phase, cyclohexane–ethyl acetate–toluene, 7.5:7.5:10 (v/v), enables acceptable resolution of nisoldipine, in large excess, and possible impurities. Regression coefficients (r 0.997), recovery (98–108%), and determination limit (0.02–0.2%) were validated and found to be satisfactory. The method is convenient for quantitative analysis and purity control of nisoldipine in its raw material and dosage forms.     

A novel ion-pairing chromatographic method for the simultaneous determination of both nicarbazin components in feed additives: chemometric tools for improving the optimization and validation

The development, optimization and validation of an ion-pairing high performance liquid chromatography method for the simultaneous determination of both nicarbazin (NIC) components: 4,4′-dinitrocarbanilide (DNC) and 2-hydroxy-4,6-dimethylpyrimidine (HDP) in bulk materials and feed additives are described. An experimental design was used for the optimization of the chromatographic system. Four variables, including mobile phase composition and oven temperature, were analyzed through a central composite design exploring their contribution to analyte separation. Five responses: peak resolutions, HDP capacity factor, HDP tailing and analysis time, were modelled by using the response surface methodology and were optimized simultaneously by implementing the desirability function. The optimum conditions resulted in a mobile phase consisting of 10.0 mmol L⁻¹ of 1-heptanesulfonate, 20.0 mmol L⁻¹ of sodium acetate, pH = 3.30 buffer and acetonitrile in a gradient system at a flow rate of 1.00 mL min⁻¹. Column was an INERSTIL ODS-3 (4.6 mm × 150 mm, 5 μm particle size) at 40.0 °C. Detection was performed at 300 nm by a diode array detector. The validation results of the method indicated a high selectivity and good precision characteristics, with RSD less than 1.0% for both components, both in intra and inter-assay precision studies. Linearity was proved for a range of 32.0-50.0 μg mL⁻¹ of NIC in sample solution. The recovery, studied at three different fortification levels, varied from 98.0 to 101.4 for HDP and from 99.1 to 100.2 for DNC. The applicability of the method was demonstrated by determining DNC and HDP content in raw materials and commercial formulations used for coccidiosis prevention. Assays results on real samples showed that considerable differences in molecular ratio DNC:HDP exist among them.     

Development of Novel Stability-Indicating Method for the Determination of Dimethindene Maleate and Its Impurities

A novel and selective stability-indicating liquid chromatographic method has been developed and validated for the analysis of dimethindene maleate, the related substance 2-ethylpyridine, and three degradation products. Dimethindene maleate was subjected to forced degradation study by acid and basic hydrolysis, oxidation, and thermal decomposition. Three degradation products that were formed during the forced degradation study were separated from dimethindene using a Zorbax SB CN column (150 × 4.6 mm; 5 μm); cyanopropyl-bonded stationary phase was applied for the first time for the separation of dimethindene and its impurities. The proposed method was validated and was found suitable for quality control and stability tests of pharmaceuticals containing dimethindene maleate.     

Development of Novel Stability-Indicating Method for the Determination of Dimethindene Maleate and Its Impurities

A novel and selective stability-indicating liquid chromatographic method has been developed and validated for the analysis of dimethindene maleate, the related substance 2-ethylpyridine, and three degradation products. Dimethindene maleate was subjected to forced degradation study by acid and basic hydrolysis, oxidation, and thermal decomposition. Three degradation products that were formed during the forced degradation study were separated from dimethindene using a Zorbax SB CN column (150 × 4.6 mm; 5 μm); cyanopropyl-bonded stationary phase was applied for the first time for the separation of dimethindene and its impurities. The proposed method was validated and was found suitable for quality control and stability tests of pharmaceuticals containing dimethindene maleate.

     

化学反应—气相色谱法测定蔬菜中杀虫双残留量

本文介绍了一种运用化学反应转化，气相色谱法快速测定蔬菜中杀虫双残留量的方法，其检测限为０．０１ｍｇ／ｋｇ。     

Development and Validation of a Liquid Chromatographic Method for Determination of Efavirenz in Human Plasma

A simple, rapid, and sensitive high-performance liquid chromatographic method for estimation of efavirenz in human plasma has been developed and validated. Chromatography was performed with C₁₈ analytical column and 50:50 acetonitrile–phosphate buffer (pH 3.5) as mobile phase. Compounds were monitored by UV detection at 247 nm. The retention time for efavirenz was 6.45 min and that for the internal standard, nelfinavir, was 2.042 min. Response was a linear over the concentration range of 0.1 μg–10 μg mL⁻¹ in human plasma. The method was simple, specific, precise and accurate and was useful for bioequivalence and pharmacokinetic studies of efavirenz.     

Comparison of Chromatographic Methods for the Determination of Bound Glycerol in Biodiesel

An important fuel criterion for biodiesel is bound glycerol, which is a function of the residual amount of triglycerides and partial glycerides in the biodiesel. Either high-temperature gas chromatography or high performance liquid chromatography can be used for determining these minor but important components in biodiesel. In this paper we have conducted a statistical study on the accuracy of the two methods for ascertaining the bound glycerol in biodiesel fuels obtained from different feedstocks. Analysis of variance showed that with one exception, namely diacylglycerols in some soy oil based biodiesel, there was no statistical difference in bound glycerol for the biodiesel samples analyzed or a difference between methods. Operationally, the high performance liquid chromatographic method is superior to the high temperature gas chromatographic method in that it requires no sample derivatization, has shorter analysis times, and is directly applicable to most biodiesel fuels.     

Reversed-Phase High Performance Liquid Chromatographic and Thin Layer Chromatographic Methods for the Simultaneous Determination of Benazepril Hydrochloride and Hydrochlorothiazide in Cibadrex Tablets

ABSTRACT

Two procedures were developed for simultaneous determination of benazepril hydrochloride (I) and hydrochlorothiazide (II) in pure, laboratory made mixtures and in pharmaceutical dosage form “Cibadrex tablets® using reversed phase high performance liquid chromatographic and thin layer chromatographic methods.

For reversed phase HPLC, a new very sensitive, rapid, selective method was developed. The linearity ranges were 32-448 ng/20 μl and 40-560 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide, respectively. The corresponding recoveries were 99.38 ± 1.526 and 99.2 ± 1.123.

The minimum detection limits were 7 ng/20 μl and 14 ng/20 μl for benazepril hydrochloride and hydrochlorothiazide respectively.

On the other hand, a new, simple, sensitive and fast thin layer chromatographic scanning densitometric method was developed for simultaneous determination of benazepril hydrochloride and hydrochlorothiazide using ethyl acetate: methanol: ammonia (85: 20: 10 v/v) as the developing system. The R_f values were 0.33 & 0.68 for benazepril hydrochloride and hydrochlorothiazide respectively. The minimum detection limit obtained was 0.12 μg/spot for benazepril hydrochloride and 0.24 μg/spot for hydrochlorothiazide. The mean percentage recoveries were 100.04 ± 1.102 and 99.31 ± 1.009 for benazepril hydrochloride and hydrochlorothiazide respectively.

The two proposed methods were simple, precise, sensitive and could be successfully applied for the determination of pure, laboratory made mixtures and pharmaceutical dosage forms. The results obtained were compared with those obtained by A ^1%.     

Determination of Lercanidipine Hydrochloride and Its Impurities in Tablets

The reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for determination of lercanidipine hydrochloride and its synthetic impurities, degradation and oxidative products in Carmen^® tablets. The best separation was performed on Zorbax SB C18 column, 250 x 4.6 mm, particle size 5 m. Acetonitrile-water-triethylamine 55:44.8:0.2 (v/v/v) was used as a mobile phase with flow rate 1 mL min^–1. pH was adjusted to 3.0 with orthophosphoric acid. UV detection was performed at 240 nm. Duration of chromatographic run was about 12 min for six examined compounds. The chromatographic conditions for the determination of lercanidipine hydrochloride and its related substances were the same, but the concentration of lercanidipine hydrochloride was 0.03 mg mL^–1 for assay and 0.3 mg mL^–1 for related substances. The validation of the method performance characteristics (figures of merits, quality of parameters) was established to be adequate for the intended use. The evaluation of number of parameters, such as selectivity, linearity, accuracy, specificity, precision (repetability and reproducibility), sensitivity and detection and determination limits is entailed.Acknowledgements This work was supported by the Institute of Pharmacy of Serbia, Belgrade and by the Ministry for Science, Technology and Development of Serbia, Contact: 1458     

快速气相色谱法测定蔬菜中菊酯类农药残留量

采用一种较快速，简单的方法测定蔬菜中菊酯类农药残留物。样本中农残经乙酸酯萃取，凝胶渗透色谱及固相提取净化后，用气相色谱－电子捕获检测器测定，色谱柱为ＨＰ－５小口长石英毛细管柱。本法对６种常用菊酯类农药的回收率范围为８９．６％－９９．７％，检测限为０．０４ｍｇ／ｋｇ。对同一批普施用菊酯类农药的白菜样本进行化验，本法跟美国食物及药品管理局农药残留标准测定方法所得结果非常吻合。