Loading…
Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry
Rationale The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS. Methods...
Saved in:
| Published in: | Rapid communications in mass spectrometry 2019-11, Vol.33 (21), p.1643-1651 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43 |
| container_end_page | 1651 |
| container_issue | 21 |
| container_start_page | 1643 |
| container_title | Rapid communications in mass spectrometry |
| container_volume | 33 |
| creator | Ntshangase, Sphamandla Mdanda, Sipho Naicker, Tricia Kruger, Hendrik G. Baijnath, Sooraj Govender, Thavendran |
| description | Rationale
The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS.
Methods
The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague–Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix‐assisted laser desorption/ionization (MALDI) MSI.
Results
LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain of 54.5 ng/g. MALDI‐MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex.
Conclusions
LC/MS/MS and MALDI‐MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI‐MSI for direct visualization of pharmaceutical drugs in situ. |
| doi_str_mv | 10.1002/rcm.8510 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2309211076</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2309211076</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43</originalsourceid><addsrcrecordid>eNp1kU1O5DAQhS0EguZH4gQjS2zYhC47SSeZHWrxJ4GQgH3ktsuNURIH22GmWXEErsYVOAluGmYzYmHZpfreK9uPkH0GRwyAj51sj8qcwRoZMaiKBHjK1skIqpwlGavKLbLt_QMAYzmHTbKVMp5BURQj8nbbi2BEQ5XxwZnZEIztqNUUmycTcO7Ek3FUdIoG7Ky2y8p01IlAZ07EUzDeD_ibHvd9Y6T4lrciuv19f3kV3kdnVLQRHh1V6K3rl9Q4LvO8ErSRor5HGZxtMbgFNa2Ym27-Obkxj4NRVN7Hpgg23qm_X4xDbGH7v3SXbGjReNz72nfI3enJ3fQ8ubw-u5geXyYyzSpItGBSSS0nEyx5WaBWVSFLXpSYQ6z4BARoneXAMolcVXnGM63jD1ZaSpGlO-RgZds7-zigD_WDHVwXJ9Y8hYozBsUkUocrSjrrvUNd9y4-zS1qBvUyujpGVy-ji-ivL8Nh1qL6B35nFYFkBfwxDS5-NKpvplefhh8QtKtt</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2309211076</pqid></control><display><type>article</type><title>Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry</title><source>Wiley</source><creator>Ntshangase, Sphamandla ; Mdanda, Sipho ; Naicker, Tricia ; Kruger, Hendrik G. ; Baijnath, Sooraj ; Govender, Thavendran</creator><creatorcontrib>Ntshangase, Sphamandla ; Mdanda, Sipho ; Naicker, Tricia ; Kruger, Hendrik G. ; Baijnath, Sooraj ; Govender, Thavendran</creatorcontrib><description>Rationale
The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS.
Methods
The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague–Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix‐assisted laser desorption/ionization (MALDI) MSI.
Results
LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain of 54.5 ng/g. MALDI‐MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex.
Conclusions
LC/MS/MS and MALDI‐MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI‐MSI for direct visualization of pharmaceutical drugs in situ.</description><identifier>ISSN: 0951-4198</identifier><identifier>EISSN: 1097-0231</identifier><identifier>DOI: 10.1002/rcm.8510</identifier><identifier>PMID: 31240777</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Anti-Retroviral Agents - chemistry ; Anti-Retroviral Agents - pharmacokinetics ; Antiretroviral drugs ; Brain ; Brain - diagnostic imaging ; Brain - metabolism ; Brain Chemistry ; Central nervous system ; Cerebral cortex ; Chromatography ; Chromatography, Liquid - methods ; Deposition ; Desorption ; Drug delivery systems ; Female ; Ionization ; Ions ; Liquid chromatography ; Mass spectrometry ; Neuroimaging - methods ; Penetration ; Pharmaceuticals ; Quinolones - chemistry ; Quinolones - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Scientific imaging ; Spatial distribution ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods ; Spectroscopy ; Tandem Mass Spectrometry - methods ; Tenofovir - chemistry ; Tenofovir - pharmacokinetics ; Tissue Distribution</subject><ispartof>Rapid communications in mass spectrometry, 2019-11, Vol.33 (21), p.1643-1651</ispartof><rights>2019 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43</citedby><cites>FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43</cites><orcidid>0000-0003-0606-2053 ; 0000-0001-7860-1779</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31240777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ntshangase, Sphamandla</creatorcontrib><creatorcontrib>Mdanda, Sipho</creatorcontrib><creatorcontrib>Naicker, Tricia</creatorcontrib><creatorcontrib>Kruger, Hendrik G.</creatorcontrib><creatorcontrib>Baijnath, Sooraj</creatorcontrib><creatorcontrib>Govender, Thavendran</creatorcontrib><title>Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry</title><title>Rapid communications in mass spectrometry</title><addtitle>Rapid Commun Mass Spectrom</addtitle><description>Rationale
The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS.
Methods
The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague–Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix‐assisted laser desorption/ionization (MALDI) MSI.
Results
LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain of 54.5 ng/g. MALDI‐MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex.
Conclusions
LC/MS/MS and MALDI‐MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI‐MSI for direct visualization of pharmaceutical drugs in situ.</description><subject>Animals</subject><subject>Anti-Retroviral Agents - chemistry</subject><subject>Anti-Retroviral Agents - pharmacokinetics</subject><subject>Antiretroviral drugs</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Brain Chemistry</subject><subject>Central nervous system</subject><subject>Cerebral cortex</subject><subject>Chromatography</subject><subject>Chromatography, Liquid - methods</subject><subject>Deposition</subject><subject>Desorption</subject><subject>Drug delivery systems</subject><subject>Female</subject><subject>Ionization</subject><subject>Ions</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Neuroimaging - methods</subject><subject>Penetration</subject><subject>Pharmaceuticals</subject><subject>Quinolones - chemistry</subject><subject>Quinolones - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Scientific imaging</subject><subject>Spatial distribution</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><subject>Spectroscopy</subject><subject>Tandem Mass Spectrometry - methods</subject><subject>Tenofovir - chemistry</subject><subject>Tenofovir - pharmacokinetics</subject><subject>Tissue Distribution</subject><issn>0951-4198</issn><issn>1097-0231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kU1O5DAQhS0EguZH4gQjS2zYhC47SSeZHWrxJ4GQgH3ktsuNURIH22GmWXEErsYVOAluGmYzYmHZpfreK9uPkH0GRwyAj51sj8qcwRoZMaiKBHjK1skIqpwlGavKLbLt_QMAYzmHTbKVMp5BURQj8nbbi2BEQ5XxwZnZEIztqNUUmycTcO7Ek3FUdIoG7Ky2y8p01IlAZ07EUzDeD_ibHvd9Y6T4lrciuv19f3kV3kdnVLQRHh1V6K3rl9Q4LvO8ErSRor5HGZxtMbgFNa2Ym27-Obkxj4NRVN7Hpgg23qm_X4xDbGH7v3SXbGjReNz72nfI3enJ3fQ8ubw-u5geXyYyzSpItGBSSS0nEyx5WaBWVSFLXpSYQ6z4BARoneXAMolcVXnGM63jD1ZaSpGlO-RgZds7-zigD_WDHVwXJ9Y8hYozBsUkUocrSjrrvUNd9y4-zS1qBvUyujpGVy-ji-ivL8Nh1qL6B35nFYFkBfwxDS5-NKpvplefhh8QtKtt</recordid><startdate>20191115</startdate><enddate>20191115</enddate><creator>Ntshangase, Sphamandla</creator><creator>Mdanda, Sipho</creator><creator>Naicker, Tricia</creator><creator>Kruger, Hendrik G.</creator><creator>Baijnath, Sooraj</creator><creator>Govender, Thavendran</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0003-0606-2053</orcidid><orcidid>https://orcid.org/0000-0001-7860-1779</orcidid></search><sort><creationdate>20191115</creationdate><title>Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry</title><author>Ntshangase, Sphamandla ; Mdanda, Sipho ; Naicker, Tricia ; Kruger, Hendrik G. ; Baijnath, Sooraj ; Govender, Thavendran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Anti-Retroviral Agents - chemistry</topic><topic>Anti-Retroviral Agents - pharmacokinetics</topic><topic>Antiretroviral drugs</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Brain Chemistry</topic><topic>Central nervous system</topic><topic>Cerebral cortex</topic><topic>Chromatography</topic><topic>Chromatography, Liquid - methods</topic><topic>Deposition</topic><topic>Desorption</topic><topic>Drug delivery systems</topic><topic>Female</topic><topic>Ionization</topic><topic>Ions</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Neuroimaging - methods</topic><topic>Penetration</topic><topic>Pharmaceuticals</topic><topic>Quinolones - chemistry</topic><topic>Quinolones - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Scientific imaging</topic><topic>Spatial distribution</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</topic><topic>Spectroscopy</topic><topic>Tandem Mass Spectrometry - methods</topic><topic>Tenofovir - chemistry</topic><topic>Tenofovir - pharmacokinetics</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ntshangase, Sphamandla</creatorcontrib><creatorcontrib>Mdanda, Sipho</creatorcontrib><creatorcontrib>Naicker, Tricia</creatorcontrib><creatorcontrib>Kruger, Hendrik G.</creatorcontrib><creatorcontrib>Baijnath, Sooraj</creatorcontrib><creatorcontrib>Govender, Thavendran</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Rapid communications in mass spectrometry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ntshangase, Sphamandla</au><au>Mdanda, Sipho</au><au>Naicker, Tricia</au><au>Kruger, Hendrik G.</au><au>Baijnath, Sooraj</au><au>Govender, Thavendran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry</atitle><jtitle>Rapid communications in mass spectrometry</jtitle><addtitle>Rapid Commun Mass Spectrom</addtitle><date>2019-11-15</date><risdate>2019</risdate><volume>33</volume><issue>21</issue><spage>1643</spage><epage>1651</epage><pages>1643-1651</pages><issn>0951-4198</issn><eissn>1097-0231</eissn><abstract>Rationale
The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS.
Methods
The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague–Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix‐assisted laser desorption/ionization (MALDI) MSI.
Results
LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain of 54.5 ng/g. MALDI‐MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex.
Conclusions
LC/MS/MS and MALDI‐MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI‐MSI for direct visualization of pharmaceutical drugs in situ.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31240777</pmid><doi>10.1002/rcm.8510</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0606-2053</orcidid><orcidid>https://orcid.org/0000-0001-7860-1779</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0951-4198 |
| ispartof | Rapid communications in mass spectrometry, 2019-11, Vol.33 (21), p.1643-1651 |
| issn | 0951-4198 1097-0231 |
| language | eng |
| recordid | cdi_proquest_journals_2309211076 |
| source | Wiley |
| subjects | Animals Anti-Retroviral Agents - chemistry Anti-Retroviral Agents - pharmacokinetics Antiretroviral drugs Brain Brain - diagnostic imaging Brain - metabolism Brain Chemistry Central nervous system Cerebral cortex Chromatography Chromatography, Liquid - methods Deposition Desorption Drug delivery systems Female Ionization Ions Liquid chromatography Mass spectrometry Neuroimaging - methods Penetration Pharmaceuticals Quinolones - chemistry Quinolones - pharmacokinetics Rats Rats, Sprague-Dawley Scientific imaging Spatial distribution Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods Spectroscopy Tandem Mass Spectrometry - methods Tenofovir - chemistry Tenofovir - pharmacokinetics Tissue Distribution |
| title | Spatial distribution of elvitegravir and tenofovir in rat brain tissue: Application of matrix‐assisted laser desorption/ionization mass spectrometry imaging and liquid chromatography/tandem mass spectrometry |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T02%3A57%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Spatial%20distribution%20of%20elvitegravir%20and%20tenofovir%20in%20rat%20brain%20tissue:%20Application%20of%20matrix%E2%80%90assisted%20laser%20desorption/ionization%20mass%20spectrometry%20imaging%20and%20liquid%20chromatography/tandem%20mass%20spectrometry&rft.jtitle=Rapid%20communications%20in%20mass%20spectrometry&rft.au=Ntshangase,%20Sphamandla&rft.date=2019-11-15&rft.volume=33&rft.issue=21&rft.spage=1643&rft.epage=1651&rft.pages=1643-1651&rft.issn=0951-4198&rft.eissn=1097-0231&rft_id=info:doi/10.1002/rcm.8510&rft_dat=%3Cproquest_cross%3E2309211076%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3490-fa1cdcfc66e8287efd97c8278e507ef260a0ff45014ce2d95424ff0119fcca43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2309211076&rft_id=info:pmid/31240777&rfr_iscdi=true |