Chromatographia最新文献_第9页

Leveraging Principles of QbD for Analytical Method Development and Validation for the Estimation of Eltrombopag Olamine in Tablet Dosage Forms by HPLC 利用 QbD 原则开发和验证高效液相色谱法估算片剂中艾曲波帕格-奥拉明的分析方法

IF 1.2 4区化学

Chromatographia Pub Date : 2024-08-12 DOI: 10.1007/s10337-024-04356-6

Nandan Godani, Saradhkumar Mudaliar, Rohan Pai, Sanjay Sharma

{"title":"Leveraging Principles of QbD for Analytical Method Development and Validation for the Estimation of Eltrombopag Olamine in Tablet Dosage Forms by HPLC","authors":"Nandan Godani, Saradhkumar Mudaliar, Rohan Pai, Sanjay Sharma","doi":"10.1007/s10337-024-04356-6","DOIUrl":"10.1007/s10337-024-04356-6","url":null,"abstract":"<div><p>The primary objective of this study is to implicate the Quality by Design (QbD) principle to develop a simple and stability—indicating High Performance liquid Chromatography (HPLC) method for analysing and quantifying Eltrombopag olamine. Initially, a comprehensive risk assessment was conducted using an Ishikawa (fish-bone) diagram. Following this, an Analytical Target Profile (ATP) was established, with desired specification and Critical Analytical Attributes (CAAs) were identified to fulfil these requirements. Additionally, Critical Material Attributes (CMAs) and Critical Process Attributes (CPPs) were chosen, as they can influence the CAAs. Subsequently, a three-level factorial design was utilized to optimize the primary contributing factors both numerically and graphically. The validation study was performed according to International Council for Harmonisation (ICH) guidelines and forced degradation studies were performed under various stress conditions. Optimal chromatographic separation was done using a mobile phase comprising acetonitrile and water with 0.3% formic acid in both phases at a ratio of 80:20% v/v, with 1.2 mL/min flow rate and UV detection at 248 nm. The developed method exhibited high sensitivity and specificity, with a linear range of 10–70 µg/mL and a correlation coefficient (R2) of 0.9999. It demonstrated accuracy with % recovery ranging from 98–100% and the detection and quantification limits of 0.2443 µg/mL and 0.7403 µg/mL, respectively. The forced degradation studies indicated that the drug is vulnerable to all stress conditions. Overall, the developed method proves to be suitable for estimation of Eltrombopag olamine in its marketed formulation, with potential applicability for analysing it in other dosage form and various biological samples available.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 10","pages":"635 - 648"},"PeriodicalIF":1.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Congress, Conferences, and Workshops 大会、会议和研讨会

IF 1.2 4区化学

Chromatographia Pub Date : 2024-08-10 DOI: 10.1007/s10337-024-04358-4

引用次数: 0

Simultaneous UHPLC-PDA Method Development and Validation for Quantification of Quercetin and Erlotinib in Liquid Crystalline Nanoparticle Formulation and Pharmacokinetic Study 液晶纳米粒制剂中槲皮素和厄洛替尼的 UHPLC-PDA 同步定量方法开发与验证及药代动力学研究

IF 1.2 4区化学

Chromatographia Pub Date : 2024-08-08 DOI: 10.1007/s10337-024-04355-7

Naresh Kothuri, Sonia Verma, Chakradhar JVUS, Sanjay Singh, Pooja Yadav, Pavan Kumar Yadav, Amit Kashyap, Amrendra Tiwari, Deepak Sharma, Manish Kumar Chourasia

{"title":"Simultaneous UHPLC-PDA Method Development and Validation for Quantification of Quercetin and Erlotinib in Liquid Crystalline Nanoparticle Formulation and Pharmacokinetic Study","authors":"Naresh Kothuri, Sonia Verma, Chakradhar JVUS, Sanjay Singh, Pooja Yadav, Pavan Kumar Yadav, Amit Kashyap, Amrendra Tiwari, Deepak Sharma, Manish Kumar Chourasia","doi":"10.1007/s10337-024-04355-7","DOIUrl":"10.1007/s10337-024-04355-7","url":null,"abstract":"<div><p>Combining anticancer drugs and phytomolecules with anticancer activity has opened up new avenues for cancer treatment and could be a potent alternative to conventional cancer therapy. Quercetin (QUR) and Erlotinib (ERB) exhibit potential anticancer properties. However, both drugs manifest low oral bioavailability due to low aqueous solubility, and interestingly, there is not a single validated UHPLC-PDA method for quantifying QUR and ERB simultaneously. Thus, the current study aims to address pharmaceutical challenges by encapsulating the two drugs in liquid crystalline nanoparticles (LCNPs) and to develop and validate a sensitive, accurate analytical, and bioanalytical method, as per guidelines, to quantify QUR and ERB simultaneously in LCNPs. Effective chromatographic elution of QUR and ERB has been achieved using a C8 reversed-phase column with an isocratic mobile phase at a flow rate of 1 mL/min, and both drugs were detected at 252 nm wavelength. The retention time was 5.3 and 7.7 min for QUR and ERB, respectively, while LOQ was less than 0.5 µg/mL for both drugs, appropriate for monitoring therapeutic drugs in preclinical and clinical research settings. The validated method was successfully applied to estimate the %drug entrapment efficiency, %drug loading, and %drug release for the simultaneous analysis of QUR and ERB in the LCNPs. The technique investigated both drugs’ pharmacokinetic characteristics in Sprague–Dawley rats. The results were deemed reliable, and the validated method was found to be precise and accurate as per guidelines for the simultaneous estimation of QUR and ERB, which have applications in formulation development and bioanalytical studies.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 10","pages":"621 - 633"},"PeriodicalIF":1.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Correction: The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form 更正：在开发和验证用于估算注射剂型中特利加压素含量的稳定性指示型 RP-HPLC PDA 方法中采用新颖的设计质量理念

IF 1.2 4区化学

Chromatographia Pub Date : 2024-08-02 DOI: 10.1007/s10337-024-04354-8

Charumathi Salva, Rajitha Galla

引用次数: 0

Determination of HPLC–ESI–MS/MS Based Phospholipids and Sphingolipids on Dried Plasma Filter Paper with Human Colorectal Cancer 基于 HPLC-ESI-MS/MS 的人类大肠癌干血浆滤纸磷脂和鞘磷脂的测定

IF 1.2 4区化学

Chromatographia Pub Date : 2024-08-01 DOI: 10.1007/s10337-024-04353-9

Jihun Jo, Hye-Ran Yoon

{"title":"Determination of HPLC–ESI–MS/MS Based Phospholipids and Sphingolipids on Dried Plasma Filter Paper with Human Colorectal Cancer","authors":"Jihun Jo, Hye-Ran Yoon","doi":"10.1007/s10337-024-04353-9","DOIUrl":"10.1007/s10337-024-04353-9","url":null,"abstract":"<div><p>The aim of this study was to find lipid metabolite concentrations differences between healthy subjects and colorectal cancer patients. A novel high performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC–ESI–MS/MS) analytical method was developed for the analysis of nine lipid series (two sphingolipids, seven phospholipids) using the multiple reaction monitoring mode (MRM) on dried plasma spots. The extracted lipids were separated by HPLC using an Imtakt Unison UK-C8. The developed method was applied to human plasma samples obtained from healthy subjects (<i>n</i> = 40) and colorectal cancer patients (<i>n</i> = 40). A partial least squares discriminant analysis (PLS-DA) model, which is a multivariate statistical analysis method, was employed to analyse the quantitative results. The VIP score of the PLS-DA model was employed to effectively discriminate colorectal cancer patients from healthy subjects. Furthermore, a random forest classification method was employed. Through statistical processing, the lipid 18:1 Lyso PC in accordance with VIP score > 1 was identified, and four lipids in accordance with <i>p</i>-value < 0.05, 15:0–18:1 PC, 18:1 Lyso PC, 18:1 Lyso PE, and C15 Ceramide (d18:1/15:0) were identified. The results of this study corresponded to study of Zhao et al.(2007) that 18:1 LPC can be potential biomarker between normal and colorectal cancer patients. This method is expected to be practically useful due to its simple dried plasma spot use and excellent sensitivity for lipid screening when applied to various diseases, including colorectal cancer.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 10","pages":"695 - 705"},"PeriodicalIF":1.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form 在开发和验证用于估算注射剂型中特利加压素含量的稳定性指示型 RP-HPLC PDA 方法中采用新颖的设计质量理念

IF 1.2 4区化学

Chromatographia Pub Date : 2024-07-25 DOI: 10.1007/s10337-024-04352-w

Charumathi Salva, Rajitha Galla

{"title":"The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form","authors":"Charumathi Salva, Rajitha Galla","doi":"10.1007/s10337-024-04352-w","DOIUrl":"10.1007/s10337-024-04352-w","url":null,"abstract":"<div><p>The research presents a novel application of the QbD technique to develop and validate a stability-indicating method for terlipressin quantification in injection form, aligning with ICH Q2 (<i>R2</i>) guidelines using the HPLC method. Terlipressin, a synthetic drug recently approved by the FDA for treating hepatorenal syndrome, lacks an official monograph in any pharmacopeia, and the existing stability indicating methods for its quantification were limited. The primary objective is to establish a method using the QbD approach and ICH Q8 (<i>R2</i>) guidelines, emphasizing accuracy, simplicity, rapidity, and robustness. The method is optimized through the design of experiments, including response surface plots, contour plots, and overlay plots. Successful development of this method results in a shorter retention time (less than 4 min) using a SunFire C<sub>18</sub> column with dimensions 250 mm × 4.6 mm and particle size of 5µm, mobile phase consisting of acetonitrile and 0.1% orthophosphoric acid (11:89 <i>v</i>/<i>v</i>), flow rate of 1 ml/min, and the PDA detection at 216 nm, with an injection volume of 8 µl and a column heater temperature of 30 °C. This method’s total run time was 6 min, using water as a diluent. Forced degradation experiments have verified that the approach is stability-indicating for the terlipressin injection dosage form assay. The analytical method has demonstrated a linear response over the 0.25–1.5 µg/ml concentration range, exhibiting an <i>R</i><sup>2</sup> of 0.9994 and recovery percentage was 99.09–100.43%.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 9","pages":"567 - 579"},"PeriodicalIF":1.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141774549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pre-column Derivative HPLC and LC–Orbitrap-MS Analysis of Monosaccharides and Non-polysaccharides in Polygonati Rhizoma 柱前衍生 HPLC 和 LC-Orbitrap-MS 分析黄精中的单糖和非多糖类物质

IF 1.2 4区化学

Chromatographia Pub Date : 2024-07-23 DOI: 10.1007/s10337-024-04350-y

Ling Liang, Yu Li, Caiyun Peng, Luyun Ning, Gangqiang Yi, Wei Wang, Hanwen Yuan, Pingan Liu

{"title":"Pre-column Derivative HPLC and LC–Orbitrap-MS Analysis of Monosaccharides and Non-polysaccharides in Polygonati Rhizoma","authors":"Ling Liang, Yu Li, Caiyun Peng, Luyun Ning, Gangqiang Yi, Wei Wang, Hanwen Yuan, Pingan Liu","doi":"10.1007/s10337-024-04350-y","DOIUrl":"10.1007/s10337-024-04350-y","url":null,"abstract":"<div><p>Polygonati Rhizoma, as a traditional medicinal herb, possesses pharmacological effects enhancing physical strength and immunity. In this study, a systematic analysis of the monosaccharide and non-polysaccharides components in Polygonati Rhizoma was conducted using pre-column derivatization high-performance liquid chromatography (HPLC–DAD) and liquid chromatography coupled to electrostatic orbitrap high-resolution mass spectrometry (LC–Orbitrap-MS) techniques. The polysaccharides from Polygonati Rhizoma were initially extracted, hydrolyzed, and derivatized with 1-phenyl-3-methyl-5-pyrazolone (PMP), resulting in the successful detection of five monosaccharides. The high sensitivity and specificity of the HPLC–DAD method were confirmed. Furthermore, by comparing the external standard method (ESM) and the quantitative analysis of multi-components by single-marker (QAMS) revealed that D-mannose is the most abundant monosaccharide in Polygonati Rhizoma. The LC–Orbitrap-MS analysis of Polygonati Rhizoma led to the identification of 53 compounds, including organic acids, amino acids, amides, saponins, alkaloids, esters, and others. This research provided significant data for the chemical composition analysis and the pharmacological basis study of Polygonati Rhizoma.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 9","pages":"549 - 559"},"PeriodicalIF":1.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141774555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Determination of Robenacoxib in Plasma Using Reverse-Phase Liquid Chromatography 用反相液相色谱法测定血浆中的罗苯那考昔

IF 1.2 4区化学

Chromatographia Pub Date : 2024-07-23 DOI: 10.1007/s10337-024-04351-x

Sherry Cox, Melissa Fayette, David Minch, Joan Bergman

{"title":"Determination of Robenacoxib in Plasma Using Reverse-Phase Liquid Chromatography","authors":"Sherry Cox, Melissa Fayette, David Minch, Joan Bergman","doi":"10.1007/s10337-024-04351-x","DOIUrl":"10.1007/s10337-024-04351-x","url":null,"abstract":"<div><p>The aim of this paper was to present a rapid, simple, and straightforward high-performance liquid chromatography (HPLC) method for the determination of robenacoxib in plasma. Robenacoxib is a member of the COXIB group of nonsteroidal anti-inflammatory drugs developed for veterinary use. The method was validated based on the FDA Guidance for Industry: Bioanalytical Method Validation for selectivity, linearity, accuracy, precision, stability, and recovery. Methylene chloride was used in a liquid–liquid extraction that produced an average recovery of 97%. Chromatographic separation occurred on a Sunfire C<sub>18</sub> column (4.6 × 150 mm) using an isocratic combination of 0.025% trifluoroacetic acid in water and acetonitrile (50:50, v/v). Ultraviolet absorbance was measured at 275 nm and the flow rate was 1.1 mL/min. The method was linear in the concentration range of 0.1 to 50 µg/mL. The assay variability ranged from 2.2% to 9.2% while the accuracy was 100%. The lower limit of quantification for a 0.1 mL sample size was 0.1 µg/mL. The method was used for the determination of robenacoxib in plasma samples.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 9","pages":"561 - 566"},"PeriodicalIF":1.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141774597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intelligent Consensus Predictions of the Retention Index of Flavor and Fragrance Compounds Using 2D Descriptors 利用二维描述符对香精香料化合物的保留指数进行智能共识预测

IF 1.2 4区化学

Chromatographia Pub Date : 2024-07-18 DOI: 10.1007/s10337-024-04349-5

Doelima Bera, Ankur Kumar, Joyita Roy, Kunal Roy

{"title":"Intelligent Consensus Predictions of the Retention Index of Flavor and Fragrance Compounds Using 2D Descriptors","authors":"Doelima Bera, Ankur Kumar, Joyita Roy, Kunal Roy","doi":"10.1007/s10337-024-04349-5","DOIUrl":"10.1007/s10337-024-04349-5","url":null,"abstract":"<div><p>The demand for novel flavors and fragrance (F&F) compounds has increased, highlighting the need for a systematic design approach. Currently, the F&F industry relies heavily on experimental approaches without considering the potential consequences of altering the features that contribute to the fragrance of the compound. In silico approaches have great potential to identify the necessary features for creating novel F&F compounds. In the present study, Quantitative Structure–Property Relationship (QSPR) models were developed using 1208 compounds and simple 2D descriptors, focusing on the RI (retention index) as the endpoint to predict the olfactory properties of molecules. Feature selection was initially carried out by multi-layered stepwise regression followed by feature thinning using the Genetic Algorithm (GA) and optimal feature combination selection using the BSS (best subset selection) method. Final models were developed using the Partial Least Squares (PLS) method. Additionally, internal and external validation of the models was performed using different validation metrics suggesting that the developed models are reliable, predictive, reproducible, and robust. To enhance the external prediction of the developed models, an Intelligent Consensus Prediction (ICP) method was employed and <b>CM3</b> (consensus model 3) (best selection of predictions (compound-wise) from individual models) was found to provide the best predictivity. The modeling descriptors suggested that the hydrophobicity, high molecular weight, aromaticity, and presence of large-size fragments (high percentage of carbon) enhance the RI values. Conversely, polarity and hydrophilicity decrease the RI values. This study can be used to optimize the stationary phase according to the flavor and fragrance compounds to obtain the desired retention index (RI values).</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 9","pages":"581 - 595"},"PeriodicalIF":1.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and Semi-quantification of 36 Compounds from Violae herba (Zihuadiding) via UHPLC-Q-Orbitrap-MS/MS as Well as Proposal of Anti-counterfeiting Quality-Marker for Pharmacopeia 通过超高效液相色谱-Q-轨道rap-MS/MS 对紫花地丁中的 36 种化合物进行鉴定和半定量，并提出药典防伪质量标记的建议

IF 1.2 4区化学

Chromatographia Pub Date : 2024-07-04 DOI: 10.1007/s10337-024-04348-6

Shaoman Chen, Xican Li, Chunhou Li, Rongxin Cai, Ban Chen, Guihua Jiang, Yongbai Liang, Xu Chen

{"title":"Identification and Semi-quantification of 36 Compounds from Violae herba (Zihuadiding) via UHPLC-Q-Orbitrap-MS/MS as Well as Proposal of Anti-counterfeiting Quality-Marker for Pharmacopeia","authors":"Shaoman Chen, Xican Li, Chunhou Li, Rongxin Cai, Ban Chen, Guihua Jiang, Yongbai Liang, Xu Chen","doi":"10.1007/s10337-024-04348-6","DOIUrl":"10.1007/s10337-024-04348-6","url":null,"abstract":"<div><p><i>Violae herba</i> (Zihuadiding) is a common Chinese herbal medicine. The current Chinese Pharmacopeia (ChP) defines <i>Viola yedoensis</i> Makino as the sole plant origin and esculetin as its sole quality-marker (Q-marker). Esculetin, however, occurs in some counterfeits as well. This implies that current ChP criterion actually cannot recognize the counterfeits <i>of V. yedoensis</i>. The study thus created a specialized MS library using ultra-high-performance liquid chromatography with quadrupole-orbitrap tandem mass spectrometry (UHPLC-<i>Q</i>-Orbitrap-MS/MS) analysis. Through library-comparison, 36 compounds were putatively identified from <i>V. yedoensis</i>; especially, four isomers were successfully distinguished, that is, vitexin vs isovitexin and schaftoside vs isoschaftoside. The subsequent UHPLC-<i>Q</i>-Orbitrap-MS/MS semi-quantification suggested that the chemical contents of 36 compounds varied from 0.001 to 1.958% and the old Q-marker esculetin had high content (0.484 ± 0.028%). According to the relevant principles, flavonoid luteolin was proposed as the new and additional Q-marker. The proposal offers a preliminary evidence to recognize seven adulterations (or counterfeits) of <i>V. yedoensis</i>.</p></div>","PeriodicalId":518,"journal":{"name":"Chromatographia","volume":"87 9","pages":"597 - 608"},"PeriodicalIF":1.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0