Youngsuk Seo, Unyong Kim, M. Oh, Nayoung Yun, H. An
Recombinant erythropoietins (EPOs) are an important class of biotherapeutics that stimulate red blood cell produc- tion. The quality, safety, and potency of EPO variants are determined largely by their glycosylation, which makes up nearly half their mass. Thus, detailed glycomic analyses are important to assess biotherapeutic quality and establish the equivalency of bio- similar EPOs now coming to market. High-resolution mass spectrometry (MS) has recently emerged as the premier tool for gly- can analysis in EPOs. Using the accurate mass measurements provided by high-resolution MS, the compositions of even large, complex glycans can easily be determined. When combined with a nano-LC separation, differentiation of structural isomers also becomes a possibility. These components, together, provide a comprehensive picture of biotherapeutic glycosylation. In this review, we provide an overview of MS-based analytical platform for glycomic characterization of EPO biotherapeutics and bio- similars.
{"title":"MS Platform for Erythropoietin Glycome Characterization","authors":"Youngsuk Seo, Unyong Kim, M. Oh, Nayoung Yun, H. An","doi":"10.5478/MSL.2015.6.3.53","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.53","url":null,"abstract":"Recombinant erythropoietins (EPOs) are an important class of biotherapeutics that stimulate red blood cell produc- tion. The quality, safety, and potency of EPO variants are determined largely by their glycosylation, which makes up nearly half their mass. Thus, detailed glycomic analyses are important to assess biotherapeutic quality and establish the equivalency of bio- similar EPOs now coming to market. High-resolution mass spectrometry (MS) has recently emerged as the premier tool for gly- can analysis in EPOs. Using the accurate mass measurements provided by high-resolution MS, the compositions of even large, complex glycans can easily be determined. When combined with a nano-LC separation, differentiation of structural isomers also becomes a possibility. These components, together, provide a comprehensive picture of biotherapeutic glycosylation. In this review, we provide an overview of MS-based analytical platform for glycomic characterization of EPO biotherapeutics and bio- similars.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76887432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quadrupole ion trap mass analyzer with a simplified geometry, namely, the cylindrical ion trap (CIT), has been shown to be well-suited using in miniature mass spectrometry and even in mass spectrometer arrays. Computation of stability regions is of particular importance in designing and assembling an ion trap. However, solving CIT equations are rather more dif- ficult and complex than QIT equations, so, analytical and matrix methods have been widely used to calculate the stability regions. In this article we present the results of numerical simulations of the physical properties and the fractional mass resolu- tions of the confined ions in the first stability region was analyzed by the fifth order Runge-Kutta method (RKM5) at the optimum radius size for both ion traps. Because of similarity the both results, having determining the optimum radius, we can make much easier to design CIT. Also, the simulated results has been performed a high precision in the resolution of trapped ions at the optimum radius size.
{"title":"Optimum Radius Size between Cylindrical Ion Trap and Quadrupole Ion Trap","authors":"S. S. Chaharborj, S. Kiai, N. Arifin, Y. Gheisari","doi":"10.5478/MSL.2015.6.3.59","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.59","url":null,"abstract":"Quadrupole ion trap mass analyzer with a simplified geometry, namely, the cylindrical ion trap (CIT), has been shown to be well-suited using in miniature mass spectrometry and even in mass spectrometer arrays. Computation of stability regions is of particular importance in designing and assembling an ion trap. However, solving CIT equations are rather more dif- ficult and complex than QIT equations, so, analytical and matrix methods have been widely used to calculate the stability regions. In this article we present the results of numerical simulations of the physical properties and the fractional mass resolu- tions of the confined ions in the first stability region was analyzed by the fifth order Runge-Kutta method (RKM5) at the optimum radius size for both ion traps. Because of similarity the both results, having determining the optimum radius, we can make much easier to design CIT. Also, the simulated results has been performed a high precision in the resolution of trapped ions at the optimum radius size.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91365841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N-Alkyl/benzyl substituted isatin derivatives are intermediates and synthetic precursors for the preparation of biolog- ical active heterocycles. N-alkyl/benzyl isatins have showed various biological activities, such as cytotoxicity, antiviral, caspase inhibition, cannabinoid receptor 2 agonists for the treatment of neuropathic pain, etc. In this study, N-alkyl/benzyl isatin deriva- tives were synthesized from isatin and alkyl/benzyl halides in presence of K2CO3 in DMF and excellent to quantitative yields (~95%) were obtained. Isatins and benzyl-isatins were condensed with fluorescein hydrazide to form fluorescein hydrazone. All the compounds were subjected to their fragmentation behavior study using LC/MS n . N-Alkyl substituted isatin derivatives frag- mented at nitrogen-carbon (N-C) bond, hence gave daughter ion as (RN+H) + . Whereas, N-benzyl substituted isatin derivatives fragmented at carbon-carbon (C-C) bond of alkyl chain which linked with nitrogen molecules, therefore gave N-methyl frag- ments (RNCH2) + . This study demonstrated that, isatin moiety present in a small/large molecule or in a matrix of reaction mixture with/without N-alkyl/benzyl substituents can be identified by mass spectroscopic fragmentation behavior study.
n -烷基/苄基取代异黄酮衍生物是制备生物活性杂环化合物的中间体和合成前体。n -烷基/苄基isatin已显示出多种生物活性，如细胞毒性、抗病毒、半胱天冬酶抑制、大麻素受体2激动剂治疗神经性疼痛等。在DMF中，在K2CO3的存在下，以isatin和烷基/苄基卤化物为原料合成了n -烷基/苄基isatin衍生物，并获得了优良的定量产率(~95%)。Isatins和苄基Isatins与荧光素肼缩合形成荧光素腙。采用LC/MS对所有化合物的断裂行为进行了研究。n-烷基取代的isatin衍生物在氮碳(N-C)键上断裂，因此产生子离子(RN+H) +。而n-苄基取代的isatin衍生物在与氮分子连接的烷基链碳-碳(C-C)键处断裂，因此得到n-甲基片段(RNCH2) +。本研究表明，通过质谱断裂行为研究，可以识别存在于小分子/大分子或有/没有n -烷基/苄基取代基的反应混合物基质中的isatin片段。
{"title":"Synthesis and Fragmentation Behavior Study of n-alkyl/benzyl Isatin Derivatives Present in Small/Complex Molecules: Precursor for the Preparation of Biological Active Heterocycles","authors":"A. Kadi, Nasser S Al-Shakliah, A. M. Rahman","doi":"10.5478/MSL.2015.6.3.65","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.65","url":null,"abstract":"N-Alkyl/benzyl substituted isatin derivatives are intermediates and synthetic precursors for the preparation of biolog- ical active heterocycles. N-alkyl/benzyl isatins have showed various biological activities, such as cytotoxicity, antiviral, caspase inhibition, cannabinoid receptor 2 agonists for the treatment of neuropathic pain, etc. In this study, N-alkyl/benzyl isatin deriva- tives were synthesized from isatin and alkyl/benzyl halides in presence of K2CO3 in DMF and excellent to quantitative yields (~95%) were obtained. Isatins and benzyl-isatins were condensed with fluorescein hydrazide to form fluorescein hydrazone. All the compounds were subjected to their fragmentation behavior study using LC/MS n . N-Alkyl substituted isatin derivatives frag- mented at nitrogen-carbon (N-C) bond, hence gave daughter ion as (RN+H) + . Whereas, N-benzyl substituted isatin derivatives fragmented at carbon-carbon (C-C) bond of alkyl chain which linked with nitrogen molecules, therefore gave N-methyl frag- ments (RNCH2) + . This study demonstrated that, isatin moiety present in a small/large molecule or in a matrix of reaction mixture with/without N-alkyl/benzyl substituents can be identified by mass spectroscopic fragmentation behavior study.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76883182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Here, we demonstrate the use of MALDI-TOF as a fast and simple analytical approach to evaluate the DNA-binding capability of various peptides. Specifically, by varying the amino acid sequence of the peptides consisting of lysine (K) and tryptophan (W), we identified peptides with strong DNA-binding capabilities using MALDI-TOF. Mass spectrometric analysis reveals an interesting novel finding that lysine residues show sequence selective preference, which used to be considered as mediator of electrostatic interactions with DNA phosphate backbones. Moreover, tryptophan residues show higher affinity to DNA than lysine residues. Since there are numerous possible combinations to make peptide oligomers, it is valuable to introduce a simple and reliable analytical approach in order to quickly identify DNA-binding peptides.
{"title":"MALDI-TOF Analysis of Binding between DNA and Peptides Containing Lysine and Tryptophan","authors":"Seonghyun Lee, Sojeong Choe, Yeeun Oh, K. Jo","doi":"10.5478/MSL.2015.6.3.80","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.80","url":null,"abstract":"Here, we demonstrate the use of MALDI-TOF as a fast and simple analytical approach to evaluate the DNA-binding capability of various peptides. Specifically, by varying the amino acid sequence of the peptides consisting of lysine (K) and tryptophan (W), we identified peptides with strong DNA-binding capabilities using MALDI-TOF. Mass spectrometric analysis reveals an interesting novel finding that lysine residues show sequence selective preference, which used to be considered as mediator of electrostatic interactions with DNA phosphate backbones. Moreover, tryptophan residues show higher affinity to DNA than lysine residues. Since there are numerous possible combinations to make peptide oligomers, it is valuable to introduce a simple and reliable analytical approach in order to quickly identify DNA-binding peptides.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72868208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Lim, Sun-ho Han, Jong-Ho Park, Ranhee Park, Min Young Lee, Jinkyu Park, Chi-Gyu Lee, K. Song
Suitable analytical procedures for the bulk analysis of ultra-trace amounts of uranium and plutonium have been developed using multi-collector inductively coupled mass spectrometry (MC–ICP–MS). The quantification and determination of the isotopic ratios of uranium and plutonium in three simulated swipe samples, a swipe blank, and a process blank were performed to validate the analytical performance. The analytical results for the simulated swipe samples were in good agreement with the certified values, based on the measurement quality goals for the analysis of bulk environmental samples recommended by the International Atomic Energy Agency (IAEA)
{"title":"Validation of Bulk Analysis with Simulated Swipe Samples Containing Ultra-Trace Amounts of Uranium and Plutonium Using MC-ICP-MS","authors":"S. Lim, Sun-ho Han, Jong-Ho Park, Ranhee Park, Min Young Lee, Jinkyu Park, Chi-Gyu Lee, K. Song","doi":"10.5478/MSL.2015.6.3.75","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.75","url":null,"abstract":"Suitable analytical procedures for the bulk analysis of ultra-trace amounts of uranium and plutonium have been developed using multi-collector inductively coupled mass spectrometry (MC–ICP–MS). The quantification and determination of the isotopic ratios of uranium and plutonium in three simulated swipe samples, a swipe blank, and a process blank were performed to validate the analytical performance. The analytical results for the simulated swipe samples were in good agreement with the certified values, based on the measurement quality goals for the analysis of bulk environmental samples recommended by the International Atomic Energy Agency (IAEA)","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81673874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Lee, Jisun Oh, S. W. Heo, J. Moon, Jeong-Hoon Kim, Sung Goo Park, B. Park, G. Kweon, Y. Yim
Low temperature plasma (LTP) ionization mass spectrometry (MS) is one of the widely used ambient analysis methods which allows soft-ionization and rapid analysis of samples in ambient condition with minimal or no sample preparation. One of the major advantages of LTP MS is selective analysis of low-molecular weight, volatile and lowto medium-polarity analytes in a sample. On the contrary, the selectivity for particular class of compound also implies its limitation in general analysis. One of the critical factors limiting LTP ionization efficiency is poor desorption of analytes with low volatility. In this study, a home-built LTP ionization source with Peltier heating sample stage was constructed to enhance desorption and ionization efficiencies of analytes in a sample and its performance was evaluated using standard mixture containing fatty acid ethyl esters (FAEEs). It was also used to reproduce the previous bacterial identification experiment using pattern-recognition for FAEEs. Our result indicates, however, that the bacterial differentiation from FAEE pattern recognition using LTP ionization MS still has many limitations.
{"title":"Peltier heating-assisted low temperature plasma ionization for ambient mass spectrometry","authors":"H. Lee, Jisun Oh, S. W. Heo, J. Moon, Jeong-Hoon Kim, Sung Goo Park, B. Park, G. Kweon, Y. Yim","doi":"10.5478/MSL.2015.6.3.71","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.3.71","url":null,"abstract":"Low temperature plasma (LTP) ionization mass spectrometry (MS) is one of the widely used ambient analysis methods which allows soft-ionization and rapid analysis of samples in ambient condition with minimal or no sample preparation. One of the major advantages of LTP MS is selective analysis of low-molecular weight, volatile and lowto medium-polarity analytes in a sample. On the contrary, the selectivity for particular class of compound also implies its limitation in general analysis. One of the critical factors limiting LTP ionization efficiency is poor desorption of analytes with low volatility. In this study, a home-built LTP ionization source with Peltier heating sample stage was constructed to enhance desorption and ionization efficiencies of analytes in a sample and its performance was evaluated using standard mixture containing fatty acid ethyl esters (FAEEs). It was also used to reproduce the previous bacterial identification experiment using pattern-recognition for FAEEs. Our result indicates, however, that the bacterial differentiation from FAEE pattern recognition using LTP ionization MS still has many limitations.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84572571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Rehman, N. Kim, M. Choi, Zeng-wei Luo, Guangmin Yao, Yongbo Xue, Yonghui Zhang, H. Yoo
Kinsenoside is a principle bioactive compound of Anoectochilus formosanus. It exhibits various pharmacological effects such as antihyperglycemic, antioxidant, anti-inflammatory, immunostimulating, and hepatoprotective activities and has recently been developed as an antidiabetic drug candidate. In this study, as part of an in vitro pharmacokinetic study, the stability of kinsenoside in rat and human liver microsomes was evaluated. Kinsenoside was found to have good metabolic stability in both rat and human liver microsomes. These results will provide useful information for further in vivo pharmacokinetic and metabolism studies.
{"title":"Evaluation of Metabolic Stability of Kinsenoside, an Antidiabetic Candidate, in Rat and Human Liver Microsomes","authors":"S. Rehman, N. Kim, M. Choi, Zeng-wei Luo, Guangmin Yao, Yongbo Xue, Yonghui Zhang, H. Yoo","doi":"10.5478/MSL.2015.6.2.48","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.2.48","url":null,"abstract":"Kinsenoside is a principle bioactive compound of Anoectochilus formosanus. It exhibits various pharmacological effects such as antihyperglycemic, antioxidant, anti-inflammatory, immunostimulating, and hepatoprotective activities and has recently been developed as an antidiabetic drug candidate. In this study, as part of an in vitro pharmacokinetic study, the stability of kinsenoside in rat and human liver microsomes was evaluated. Kinsenoside was found to have good metabolic stability in both rat and human liver microsomes. These results will provide useful information for further in vivo pharmacokinetic and metabolism studies.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85855267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phosphorylation upon protein is well known to a key regulator that implicates in modulating many cellular processes like growth, migration, and differentiation. Up to date, grafting of multidimensional separation techniques onto advanced mass spectrometry (MS) has emerged as a promising tool for figuring out the biological functions of phosphorylation in a cell. How- ever, advanced MS-based phosphoproteomics is still challenging, due to its intrinsic issues, i.e., low stoichiometry, less suscepti- bility in positive ion mode, and low abundance in biological sample. To overcome these bottlenecks, diverse techniques (e.g., SCX, HILIC, ERLIC, IMAC, TiO2, etc.) are continuously developed for on-/off-line enrichment of phosphorylated protein (or peptide) from biological samples, thereby helping qualitative/quantitative determination of phosphorylated protein and its phos- phorylated sites. In this review, we introduce to the overall views of enrichment tools that are universally used to selectively iso- late targeted phosphorylated protein (or peptide) from ordinary ones before MS-based phospoproteomic analysis.
{"title":"Enrichment Strategies for Identification and Characterization of Phosphoproteome","authors":"Sun-Young Lee, Dukjin Kang, Jongki Hong","doi":"10.5478/MSL.2015.6.2.31","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.2.31","url":null,"abstract":"Phosphorylation upon protein is well known to a key regulator that implicates in modulating many cellular processes like growth, migration, and differentiation. Up to date, grafting of multidimensional separation techniques onto advanced mass spectrometry (MS) has emerged as a promising tool for figuring out the biological functions of phosphorylation in a cell. How- ever, advanced MS-based phosphoproteomics is still challenging, due to its intrinsic issues, i.e., low stoichiometry, less suscepti- bility in positive ion mode, and low abundance in biological sample. To overcome these bottlenecks, diverse techniques (e.g., SCX, HILIC, ERLIC, IMAC, TiO2, etc.) are continuously developed for on-/off-line enrichment of phosphorylated protein (or peptide) from biological samples, thereby helping qualitative/quantitative determination of phosphorylated protein and its phos- phorylated sites. In this review, we introduce to the overall views of enrichment tools that are universally used to selectively iso- late targeted phosphorylated protein (or peptide) from ordinary ones before MS-based phospoproteomic analysis.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89385691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This article reviews the fundamentals of sample preparation used in matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). MALDI is a soft ionization method used to generate analyte ions in their intact forms, which are then detected in MS analysis. MALDI-MS boasts fast analysis times and easy-to-use operation. The disadvantages of MALDI-MS include the occurrence of matrix-associated peaks and inhomogeneous distribution of analyte within the matrix. To overcome the disadvan- tages of MALDI-MS, various efforts have been directed such as using different matrices, novel matrix systems, various additives, and different sample preparation methods. These various efforts will be discussed in detail. This article will benefit those who would like to obtain basic knowledge of MALDI sample preparation and those who would like to use MALDI-MS in their chemical analyses.
{"title":"Sample Preparation for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry","authors":"Jeongkwon Kim","doi":"10.5478/MSL.2015.6.2.27","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.2.27","url":null,"abstract":"This article reviews the fundamentals of sample preparation used in matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). MALDI is a soft ionization method used to generate analyte ions in their intact forms, which are then detected in MS analysis. MALDI-MS boasts fast analysis times and easy-to-use operation. The disadvantages of MALDI-MS include the occurrence of matrix-associated peaks and inhomogeneous distribution of analyte within the matrix. To overcome the disadvan- tages of MALDI-MS, various efforts have been directed such as using different matrices, novel matrix systems, various additives, and different sample preparation methods. These various efforts will be discussed in detail. This article will benefit those who would like to obtain basic knowledge of MALDI sample preparation and those who would like to use MALDI-MS in their chemical analyses.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73221514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roflumilast analogs are a group of drugs which act as selective photodiesterase (PDE-4) inhibitor for the treatment severe chronic pulmonary disease associated with chronic brochnonities. Structural identification of degradation products using high resolu- tion mass spectrometry and theoretical investigation by density functional theory have been successfully carried out on roflumilast to identify four degradation products namely, 3,5-dichloropyridin-4-amine, N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)-3-hydroxy benzamide, N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy) benzamide and 3-(cyclopropylmethoxy)-N- (3,5-dichloro-1-oxidopyridin-4-yl)-4-(difluoro methoxy) benzamide, generated in alkali, acidic and oxidative conditions.
{"title":"Identification of Degradation Products in the Phosphodiesterase (PDE-4) Inhibitor Roflumilast Using High Resolution Mass Spectrometry and Density Functional Theory Calculations","authors":"S. K. Paul, Upendra N. Dash","doi":"10.5478/MSL.2015.6.2.38","DOIUrl":"https://doi.org/10.5478/MSL.2015.6.2.38","url":null,"abstract":"Roflumilast analogs are a group of drugs which act as selective photodiesterase (PDE-4) inhibitor for the treatment severe chronic pulmonary disease associated with chronic brochnonities. Structural identification of degradation products using high resolu- tion mass spectrometry and theoretical investigation by density functional theory have been successfully carried out on roflumilast to identify four degradation products namely, 3,5-dichloropyridin-4-amine, N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)-3-hydroxy benzamide, N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy) benzamide and 3-(cyclopropylmethoxy)-N- (3,5-dichloro-1-oxidopyridin-4-yl)-4-(difluoro methoxy) benzamide, generated in alkali, acidic and oxidative conditions.","PeriodicalId":18238,"journal":{"name":"Mass Spectrometry Letters","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79511281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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