Application of Multicriteria Methodology in the Development of Improved RP-LC-DAD for Determination of Rizatriptan and Its Degradation Products

The aim of this study was to establish an improved isocratic RP-LC-DAD method for separation and determination of rizatriptan benzoate and its two degradation products, L-749.019 and L-783.540 in tablets. Since the chromatographic behavior of target substances can be influenced by various experimental parameters, the whole study was carried out by employing experimental design methodology. The investigation included the influence of mutual changes of the mobile phase composition (methanol amount in the range 3–7% and pH of the water phase from 5.0 to 6.0) and the temperature (from 20 to 30 °C). The response surface design by means of Box-Brehnken design was used to obtain a predictive model which describes the changes in the response within the experimental domain. Additionally, several different target responses were evaluated and Derringer’s desirability function was used for reaching a suitable compromise among the responses. This multi-criteria decision making approach is based on constructing a desirability function for each individual response and afterwards establishing the overall desirability function. Such methodology provided us with the best operating conditions, satisfactory resolutions between the analytes and the shortest possible total analysis time. The experiments were performed on C₁₈ XTerra (150 mm × 3.9 mm), 5 μm column with the mobile phase consisting of a mixture of methanol, TEA and 0.01 mol L^?1 KH₂PO₄ (6:9.4:84.6 v/v) pumped at a flow rate of 1.2 mL min^?1, pH of the water phase adjusted to 6 with 85% orthophosphoric acid, a column temperature of 20 °C and detection at 225 nm. Afterwards, the new method was validated and subsequently applied in analysis of commercially available rizatriptan tablets.     

Development of Advanced Chemometric-Assisted Spectrophotometric Methods for the Determination of Cromolyn Sodium and Its Alkaline Degradation Products

Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and its alkaline degradation products (Deg1 and Deg2). Spectrophotometric mean centering ratio spectra method (MCR) and chemometric methods, including principal component regression (PCR) and partial least square (PLS-2) methods, were applied. Peak amplitudes after MCR at 367.8 nm, 373.8 nm and 310.6 nm were used within linear concentration ranges of 2–40 µg mL⁻¹, 5–40 µg mL⁻¹ and 10–100 µg mL⁻¹ for CS, Deg1 and Deg2, respectively. For PCR and PLS-2 models, a calibration set of eighteen mixtures and a validation set of seven mixtures were built for the simultaneous determination of CS, Deg1 and Deg2 in the ranges of 5–13 µg mL⁻¹, 8–16 µg mL⁻¹, and 10–30 µg mL⁻¹, respectively. The authors emphasize the importance of a stability-indicating strategy for the investigation of pharmaceutical products.     

Validated Stability-Indicating Chromatographic Methods for the Determination of Veralipride in Presence of Its Degradation Products

Two sensitive and selective chromatographic methods were developed and validated for determination of veralipride in presence of its degradation products. Forced degradation studies were performed, using HCl, NaOH and 3% H₂O₂. The first method is based on thin-layer chromatographic separation of the intact drug spot from its degradation, followed by densitometric measurements. The second method is based on isocratic liquid chromatographic separation of the studied drug from its degradation on a reversed phase C₁₈ column. The proposed LC method was utilized to investigate the kinetics of alkaline degradation process of the selected drug at different temperatures.     

Stability-Indicating Method For The Determination Of N-Desmethyldiazepam And Simultaneous Determination Of Its Degradation Products

Abstract

A simple, direct and sensitive spectrophotometric method for the determination of the intact N-desmethyldiazepam in the presence of its degradation products, 2-amino-5-chlorobenzophenone and glycine, is developed. The proposed procedure is based on direct measurement of the absorbance of its acidified methanolic solution at 361 nm. The procedure determines 8–56 mcg ml^?1 of N-desmethyldiazepam with an accuracy of 100.2 ± 0.51%. The proposed procedure retains its accuracy in presence of up to 80% of the different degradation products. The procedure is applied successfully for the determination of N-desmethyldiazepam in bulk powder, tablets and drops.

Simultaneous determination of the different degradation products in the presence of the parent drug is also described. Thus, 2-amino-5-chlorobenzophenone is determined by direct measurement of its methanolic solution at about 380 nm, with an accuracy of 100.4 ± 0.42%. Glycine is determined colorimetrically using ninhydrin reagent in presence of pyridine, with an accuracy of 99.5 ± 0.78%.     

UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form

A simple, rapid, isocratic, stability-indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed and validated for the routine analysis of moxonidine in the presence of its degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms. Forced degradation studies were performed according to the guidance of International Conference for Harmonization and were used to evaluate moxonidine intrinsic stability. The drug was subjected to acid, neutral and base hydrolysis as well as to oxidative, thermal and photolytic decomposition in both solution and solid state. The drug appeared to be unstable towards acid and base hydrolysis. To achieve desirable conditions for UPLC analysis, the method development was done with the assistance of experimental design and multivariate optimization methodology by means of Derringer’s desirability function. Stress samples were analyzed according to the experimental plan for fractional factorial screening design and Box-Behnken optimization design. The chromatographic separation was achieved on a C₁₈ Hypersil Gold aq. column (100 mm × 2.1 mm, 1.9 μm) with the mobile phase consisting of methanol–ammonium acetate buffer (10 mM, pH 3.43) mixture (0.9:99.1, v/v) pumped at a flow rate of 870 μL min^?1 and detection wavelength of 255 nm. The UPLC–MS and UPLC–MS/MS analyses were further used to characterize the found degradation products. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial tablets.     

TLC-Densitometric Determination of Tenoxicam and Its Degradation Products in Pharmaceutical Preparations and after Hydrolysis in Solutions

JPC – Journal of Planar Chromatography – Modern TLC - A direct, rapid, and sensitive thin-layer chromatography (TLC) method with densitometric detection was developed and validated for...     

Simultaneous Determination of Pyridine-Triphenylborane Anti-Fouling Agent and Its Degradation Products in Artificial Seawater by CZE

We developed a CZE method for simultaneous determination of pyridine-triphenylborane (PTPB) anti-fouling agent and its degradation products such as diphenylborinic acid (DPB), phenylboronic acid (MPB), and phenol in artificial seawater (ASW) with no extraction procedure. The ASW samples, in which 20 % (v/v) acetonitrile was added, were injected directly into the capillary using vacuum injection. As the background electrolyte, 60 mM sodium tetraborate adjusted to pH 9.8 was used. The LODs (S/N = 3) for PTPB, DPB, MPB, and phenol were, respectively, 55, 78, 126, and 30 μg L^?1. The RSDs (n = 4) for analytes listed above were in the respective ranges of 2.7–5.7, 0.68–6.1, and 0.69–1.1 % for the peak area, peak height, and migration time. Simple degradation experiments were conducted to verify the usefulness of the proposed method. The PTPB samples dissolved in ASW were put in the open air, and rooms with and without light. The sample solutions were analyzed over time. We inferred that PTPB in ASW was more degraded by photolysis than by hydrolysis. The proposed CZE method has been demonstrated as a useful tool to elucidate the PTPB degradation process and its degradation products in ASW.     

超高效液相色谱-串联四极杆质谱法对N-甲基氧化吗啉及其降解产物的检测

建立了N-甲基氧化吗啉(NMMO) 及其降解产物吗啉、N-甲基吗啉、N-亚硝基吗啉的超高效液相色谱-串联四极杆质谱联用的分析方法.以Waters Acquity BEH C18超高效液相色谱柱为分析柱,乙腈-氨水为梯度洗脱液,4种分析物在3 min内即可达到良好分离;经串联四极杆质谱多反应监测模式检测,4种物质的线性范围为10 ～500 μg/L,检出限为1 ～10 μg/L.考察了酸性、碱性两种流动相体系对样品的分离效果,发现碱性流动相体系的分离效果优于酸性流动相体系,同时发现质谱响应信号随着流动相pH值的增大而减小.在优化条件下,对实际样品以及加标后样品进行测定,结果满意,该方法适合大批量Lyocell纤维纺丝凝固浴等样品的测定以及NMMO的出口检测.     

Simultaneous Determination of Pyridine-Triphenylborane Anti-Fouling Agent and Its Degradation Products in Artificial Seawater by CZE

We developed a CZE method for simultaneous determination of pyridine-triphenylborane (PTPB) anti-fouling agent and its degradation products such as diphenylborinic acid (DPB), phenylboronic acid (MPB), and phenol in artificial seawater (ASW) with no extraction procedure. The ASW samples, in which 20 % (v/v) acetonitrile was added, were injected directly into the capillary using vacuum injection. As the background electrolyte, 60 mM sodium tetraborate adjusted to pH 9.8 was used. The LODs (S/N = 3) for PTPB, DPB, MPB, and phenol were, respectively, 55, 78, 126, and 30 μg L⁻¹. The RSDs (n = 4) for analytes listed above were in the respective ranges of 2.7–5.7, 0.68–6.1, and 0.69–1.1 % for the peak area, peak height, and migration time. Simple degradation experiments were conducted to verify the usefulness of the proposed method. The PTPB samples dissolved in ASW were put in the open air, and rooms with and without light. The sample solutions were analyzed over time. We inferred that PTPB in ASW was more degraded by photolysis than by hydrolysis. The proposed CZE method has been demonstrated as a useful tool to elucidate the PTPB degradation process and its degradation products in ASW.

     

反相高效液相色谱法测定阿德福韦酯及其降解产物

建立了一快速、简单地测定阿德福韦酯及其降解产物阿德福韦单特戊酸甲基酯、阿德福韦的反相高效液相色谱方法。以Inertsil CN-3化学键合硅胶为固定相,以乙腈-25 mmol/L磷酸盐缓冲液(pH 4.0)(体积比为33∶67)为流动相,流速1.0 mL/min,检测波长260 nm。阿德福韦酯、阿德福韦的质量浓度分别为1.861~181.7 mg/L和2.018~197.2 mg/L时与峰面积呈良好的线性关系(r分别为0.9999和0.9998);阿德福韦酯及阿德福韦平均加样回收率分别为99.5%~10     

土壤中莠去津及其降解产物的提取及高效液相色谱-质谱分析

建立了高效液相色谱-质谱联用(HPLC-MS)选择离子检测(SIM)分析环境土样中的痕量莠去津及其降解产物脱乙基莠去津(deethylatrazine,DEA)、脱异丙基莠去津(deisopropylatrazine,DIA)、羟基化莠去津(HA)的方法。土样用双蒸水超声提取,然后用Waters Oasis MCX固相萃取小柱富集纯化土样提取液,测得莠去津及其降解物在不同加标浓度(4.5~120 ng/g)下的回收率为：莠去津40.4%~82.0%,DEA 60.6%~86.5%,DIA 69.2%~86     

Development and Validation of Chromatographic Methods for the Quantification of Dabigatran Etexilate Mesylate in the Presence of Its Risky Degradation Products

JPC – Journal of Planar Chromatography – Modern TLC - New stability-indicating thin-layer chromatography (TLC)—densitometry and reversed-phase liquid chromatography (RP-LC)...     

腊制品食盐测定的样品处理探讨

GB／T5009．44—1996规定腊制品中食盐测定样品处理采用碳化浸出法和灰化浸出法,此两种方法在碳化时由于样品在瓷蒸发皿中加热碳化时有可能溅出,同时在碾碎碳化物时也有可能存在损失,使测定结果偏低,并且要碳化完全还比较费时。针对这些缺点,笔者在腊制品食盐浸出方面进行了探索,发现用测定腊制品中亚硝酸盐的样品处理液来测定样品中食盐含量,能够避免以上这些缺点,使检验结果精密度、准确度有所提高,并且与原法测定结果无显著差异。     

加速溶剂萃取/液相色谱-串联质谱测定底泥中氯硝柳胺及其降解产物

建立了加速溶剂萃取/液相色谱-串联质谱分析底泥中氯硝柳胺及其降解产物(5-氯水杨酸和2-氯-4-硝基苯胺)的方法。以中性氧化铝作为池内吸附材料,集提取和净化于一步,乙腈-水(3∶1,体积比)作为萃取溶剂,优化了温度和静态萃取时间等参数。在优化条件下,氯硝及其降解产物在0.1~20.0μg/L范围内有良好线性关系,相关系数(r)均大于0.999。方法的检出限和定量下限分别为0.04~0.1μg/kg和0.2~0.5μg/kg。用于底泥中氯硝柳胺及其降解产物的分析,在0.5、1.0、2.0μg/kg加标水平下,平均加标回收率为93.5%~101.9%,相对标准偏差为3.7%~6.7%。该方法简便,灵敏度高,重现性好,可应用于实际样品分析。     

Sorbic Acid and Its Degradation Products: Electrochemical Characterization

The electrochemical redox behavior of sorbic acid (SA), an important food preservative, was investigated at a glassy carbon electrode using cyclic, differential pulse, and squarewave voltammetry over a wide pH range. The oxidation of SA is an irreversible, diffusion-controlled, and pH-independent process that occurs with the transfer of only one electron and does not involve the formation of any electroactive oxidation product. Adsorption of SA at GCE electrodes was also observed. Following incubation in different pH electrolytes, the degradation of SA was electrochemically detected by the appearance of a new oxidation peak at lower potential value. The degradation products, formed homogenously in solution, undergo irreversible oxidation and lead to the formation of two oxidation products that strongly adsorb on the electrode surface and are reversibly oxidized. SA degradation was also confirmed using HPLC and UV-Vis spectrophotometry. A mechanism for oxidation of SA and its degradation products in aqueous solutions was proposed.     

Oxidized Multi-Walled Carbon Nanotubes as SPE Sorbent for Determination of Mefenacet and Its Degradation Products Residues in Water Samples by RRLC-UV-ESI-MS

A new method was developed for the analysis of herbicide mefenacet (MN) and its three photolysis degradation products namely hydroxylbenzothiazole (HBT), N-methylaniline (N-MA) and 2-benzothiazoloxyacetic acid (2-BAA) in water samples by rapid resolution liquid chromatography coupled with UV detection and electrospray ionization mass spectrometry. In the SPE pre-concentration step, the adsorptive potential of oxidized multi-walled carbon nanotubes for the extraction of these four target analytes was investigated for the first time. Parameters influencing the extraction efficiency, such as sample flow-rate, eluent volume and sample volume, were examined. The mean recoveries were between 85.6 and 101.4% and relative standard deviations were between 3.0 and 9.2%. The limits of detection obtained were 0.02 μg L^?1 for MN and 2-BAA and 0.04 μg L^?1 for HBT and N-MA. The proposed method was applied to monitor the residual concentrations of these four target analytes in 39 real water samples collected from April to July of 2009.     

Development of a New HPLC Method for Determination of Papaverine in Presence of Its Photooxidation Products

A new HPLC method was developed for determination of papaverine in a papaverine naturally photooxidized solution using a Duet C18/SCX column. The mobile phase used was a mixture of phosphate buffer (pH = 3.80) and acetonitrile in 40:60 ratio. The compounds identified were: papaverinol, papaveraldine, papaverine, and pyrrocolonium ion. Very good resolutions, peak shapes, and asymmetries were obtained. An ion exchange experiment was developed in order to identify and separate the pyrrocolonium ion. This was retained completely by a cation exchange resin in its Na⁺ form, while papaverine, papaverinol, and papaveraldine were retained more or less, due to a retention explained by a combined ion exchange-solvent extraction mechanism. Voltammetric studies showed that natural photooxidation of papaverine occurs in three irreversible steps and yields to stable compounds in solution.     

Development of the Validated Stability-Indicating Method for the Determination of Vortioxetine in Bulk and Pharmaceutical Formulation by HPLC-DAD,Stress Degradation Kinetics Studies and Detection of Degradation Products by LC-ESI-QTOF-MS

Vortioxetine (VOR) is a new antidepressant drug used to treat major depressive disorder. In this work, a novel, simple, rapid, accurate, precise, selective, stability-indicating, and fully validated high-performance liquid chromatography method with diode array detection (HPLC-DAD) was developed to determine VOR in bulk and pharmaceutical formulations. A Polar-RP column was used, with a mobile phase consisting of acetonitrile (ACN), methanol (MeOH), acetate buffer pH 3.5, and addition of diethylamine (DEA) in the isocratic elution mode. Assessing the stability of the VOR is fundamental to guarantee the efficacy, safety, and quality of drug products. In this study, the VOR active pharmaceutical ingredient (API) and tablets were subjected to a detailed study of forced degradation, using several degrading agents (acid, alkaline, water, heat, light, and oxidation agents). The developed HPLC-DAD method allows the collection of all the essential data to determine degradation kinetics. It was found that the decomposition of vortioxetine is fragile towards oxidative conditions and photolysis, yielding the first-order and second-order kinetic reaction in the above stress conditions, respectively. The degradation products (DPs) were identified by the high-resolution liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) method. The HPLC-DAD method was successfully applied for the quantification of VOR in tablets. Additionally, in silico toxicity prediction of the DPs was performed.     

便携式三聚氰胺快速检测仪的研制与应用

自主研发了便携式三聚氰胺速检仪,利用纳米增敏表面增强拉曼光谱法,定量检出限为0.5 mg/kg;采用相对测量方式可有效克服测量不稳定性.用于原奶、消毒奶、酸奶、奶粉中三聚氰胺检测,线性关系良好.样品前处理步骤简单.通常情况,平均单样检测时间小于2 min,仪器检测时间小于30 s,尤其适用于现场快速分析.除了可应用于乳...     

Determination of S-Carboxymethyl-L-Cysteine, Methylparaben and their Degradation Products in Syrup Preparations

An HPLC method was developed for the determination of S-carboxymethyl-L-cysteine, methylparaben and related compounds in cough syrup preparations. The HPLC operating conditions used were acetonitrile-methanol-water (120:280:600, V/V/V) pH adjusted to 4.0 with 0.1 M HCl, on a 5um Spherisorb ODS2 column (250 mm x 4.6 mm) with a flow rate of 1 mL min^–1. The injection volume was 10 L and absorbance was monitored at 210 nm with 0.05 a.u.f.s. sensitivity.