Frontiers in Medicinal Chemistry

Volume: 1

Mass Spectrometry Based Assays for Drug Screening in the Early Phases of Drug Discovery

Author(s): Marshall M. Siegel

Pp: 273-292 (20)

DOI: 10.2174/978160805204210401010273

* (Excluding Mailing and Handling)

Abstract

Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometric methods useful for exploratory and early discovery drug screening are reviewed. All methods described involve studies of non-covalent complexes between biopolymer receptors and small molecule ligands formed in the condensed phase. The complexes can be transferred directly into the gas phase by ESI-MS using gentle experimental conditions. Gas phase screening applications are illustrated for drug ligand candidates noncovalently interacting with peptides, proteins, RNA, and DNA. In the condensed phase, the complexes can be also isolated, denatured and analyzed by ESI-MS to identify the small molecule ligands. Condensed phase drug screening examples are illustrated for the ESI-MS ancillary techniques of affinity chromatography, ultrafiltration, ultracentrifugation, gel permeation chromatography (GPC), reversed phase-high performance liquid chromatography (RP-HPLC) and capillary electrophoretic methods. Solid phase drug screening using MALDI-MS is illustrated for small molecule ligands bound to MALDI affinity probe tips and to beads. Since ESI and MALDI principally produce molecular ions, high throughput screening is achieved by analyzing mass indexed mixtures.


Keywords: Drug screening, mass spectrometry, electrospray ionization, matrix-assisted laser desorption/ionization, proteins, peptides, DNA, RNA, non-covalent binding, biopolymer-drug complexes, affinity chromatography, affinity extraction, ultrafiltration, frontal affinity chromatography, microconcentrator, pulsed ultrafiltration, ultracentrifugation, gel permeation chromatography, spin columns, reversed phase high performance liquid chromatography, capillary electrophoresis, capillary isoelectric focusing, affinity probe tips, flow cytometry

Related Journals
Related Books
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version169msRequest Duration26MBMemory UsageGET chapter/{id}/{param?}Route
  • warninglog[23:27:04] LOG.warning: Optional parameter $id declared before required parameter $request is implic...
  • Booting (90.02ms)time
  • Application (79.01ms)time
  • 1 x Booting (53.26%)
    90.02ms
    1 x Application (46.74%)
    79.01ms
    12 templates were rendered
    • ebook.chapter_detailschapter_details.blade.php#?blade
    • layouts.chapter_header_sectionchapter_header_section.blade.php#?blade
    • ebook.chapter_top_bannerchapter_top_banner.blade.php#?blade
    • ebook.chapter_bottom_bannerchapter_bottom_banner.blade.php#?blade
    • ebook.ebook_right_bannerebook_right_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET chapter/{id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ChapterController@GetChapterDetails
    namespace
    App\Http\Controllers
    where
    as
    chapter
    file
    app/Http/Controllers/ChapterController.php:1350-1704
    19 statements were executed21.03ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316440840','',1,1739834824,1739834824) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739834824
      870μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316440840','/chapter/2276',1,1739834824,1739834824)
      150μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) limit 1
      12.71msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316440840
      • 1: 316440840
      • 2: 316440840
      • 3: 316440840
      • 4: 316440840
      • 5: 316440840
      • 6: 316440840
      • 7: 316440840
      • 8: 316440840
      • 9: 316440840
      • 10: 316440840
      • 11: 316440840
      • 12: 316440840
      • 13: 316440840
      • 14: 316440840
      • 15: 316440840
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • select * from `chapter` where `chapter_id` = '2276' limit 1
      260μsalphaeurekaselec_live_10_06_2022ChapterController.php#1406
      Bindings
      • 0: 2276
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1406
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`chapter_id` = '2276' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      560μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 2276
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ChapterController.php:1411
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `keywords` where `chapter_id` = '2276'
      280μsalphaeurekaselec_live_10_06_2022ChapterController.php#1415
      Bindings
      • 0: 2276
      Backtrace
      • 15. app/Http/Controllers/ChapterController.php:1415
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select * from `ebook` where `ebook_id` = 157 limit 1
      200μsalphaeurekaselec_live_10_06_2022ChapterController.php#1430
      Bindings
      • 0: 157
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1430
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select count(*) as aggregate from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=157) and se.ebook_id!=157 and v.ebook_status='1'
      1.09msalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 16. app/Models/Subject.php:238
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=157) and se.ebook_id!=157 and v.ebook_status='1' limit 10 offset 0
      650μsalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 14. app/Models/Subject.php:238
      • 15. app/Http/Controllers/ChapterController.php:1434
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as aggregate from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=157)
      340μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct j.nid as journal_nid,j.title,j.subtitle,j.issn,j.eissn,j.keyword,sj.journal_id,j.image_file_name,j.flyer_link from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=157) limit 10 offset 0
      400μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 14. app/Models/Subject.php:255
      • 15. app/Http/Controllers/ChapterController.php:1435
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `e`.*, `a`.*, `y`.`year`, `e`.`ebook_volume_id` as `ebook_volume_id`, `a`.`ebook_volume_id` as `ebk_vol_id`, `e`.`ebook_id` as `ebk_ebook_id` from `ebook_volume` as `e` left join `author` as `a` on `e`.`ebook_volume_id` = `a`.`ebook_volume_id` left join `year` as `y` on `y`.`id` = `e`.`year_id` where `e`.`ebook_volume_id` = 948 and `e`.`is_uploaded` = 1
      450μsalphaeurekaselec_live_10_06_2022EbookVolume.php#271
      Bindings
      • 0: 948
      • 1: 1
      Backtrace
      • 13. app/Models/EbookVolume.php:271
      • 14. app/Http/Controllers/ChapterController.php:1438
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) rcd from `ebook_volume` where `ebook_id` = 157 and ebook_volume_id <> 948 limit 1
      240μsalphaeurekaselec_live_10_06_2022EbookVolume.php#999
      Bindings
      • 0: 157
      Backtrace
      • 14. app/Models/EbookVolume.php:999
      • 15. app/Http/Controllers/ChapterController.php:1462
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '2276' and content_type = 'c' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      270μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '948' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      230μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 948) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 948) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 948)
      550μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2276) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2276) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2276)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 948 and `b`.`banner_from_date` <= 1739834824 and `b`.`banner_to_date` >= 1739834824 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.02msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 948
      • 3: 1739834824
      • 4: 1739834824
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='5735bcf8085db1a8c3666e645f72668c'
      180μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    24Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        cFyY1ptoTRTn6ugovaPXjsaHiTYFuA7yzDRvlGi9
        uc_cart_id
        5735bcf8085db1a8c3666e645f72668c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2276" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/2276
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IjV0bHN2dEtkTHM1ZVpWQm55Rko3TVE9PSIsInZhbHVlIjoiR2JqRjdwMWZ1ZjNYV0JMbzU4Qmk1SzRhcUEyRTN4MlZ6SG9tUGc0RUlTST0iLCJtYWMiOiIwYjJiMTc1NmFkN2UyZTM5ZDZlMmYwOGM4NmRmZDI2ODkwZGNlMzU1MWI2YTRmZjU5MzE2NGQyYjJlZDMwMDg3IiwidGFnIjoiIn0%3D; XSRF-TOKEN=eyJpdiI6ImVMdjU4VU9tcm5yZ2pjVmtTb2J4U0E9PSIsInZhbHVlIjoiUzFJZXAvQkJLNlVXVlU4NTNoNE1mTmhDU2M5VlU3TWtZZU92Ym1QYjJWS2d1N1dmV0tBSjdVMXFYL2Y1V2l6eDNlaXVXV0l3N3VDMk9IN2ZZeklqVktWY1FNOXhYNmFqRmp6Rjlwamk0M1hmWm5Bcm41VVhCKzNlTGVNVTVvamMiLCJtYWMiOiIyYTA5YmY2ZTE3ODQyZGQzZmI4ODQxZjNmMjM2NzgwM2UwOWYwZDY4ODhjZjA3MGQ2MDY5Yjc0ODAzZDY0MTg1IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IlgrcnhmZ3IzNnppVVhNUFZWVUJxYXc9PSIsInZhbHVlIjoiZ0RkMWJXNTY3dmsxcDFBREVYLzBsTHQ4L3gvT25tdlFoTC83YXJqSkJMbkVCUXdwN0JoQ05HaFlBS2JzL2xuVW1BdVVlTzFGSnE3NGhYZnUzenNrSW5ZbHhaY2lZUVhRWExRNzMvdnNINW1PQy94ckN3cGJhUXE1OFNFVDVxUW8iLCJtYWMiOiJkMTgxNmNhNGMwNDBlMDU4MjBmNzJmZWZmOTI1ZTFjNzJhMjA0MjA5YzBiNTEyMDczM2E5Mzc1NTljMTViZWY1IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjV0bHN2dEtkTHM1ZVpWQm55Rko3TVE9PSIsInZhbHVlIjoiR2JqRjdwMWZ1ZjNYV0JMbzU4Qmk1SzRhcUEyRTN4MlZ6SG9tUGc0RUlTST0iLCJtYWMiOiIwYjJiMTc1NmFkN2Uy" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:3 [ "wayfindertarget" => null "XSRF-TOKEN" => "cFyY1ptoTRTn6ugovaPXjsaHiTYFuA7yzDRvlGi9" "alphaeurekaselectnet_session" => "7oK6jcEe2ES8ypI3PdfRDnLkHZXamtsETZWzqTzJ" ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:27:04 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlpXQlNBYXhUK2t2MkRzazdWUHFpeXc9PSIsInZhbHVlIjoiRnNuWUZmQ3BNbXFxQ1FIeWM3UWpLTERoZHZvTEFxTm1Ibk9VdXRhR3Rsa2tieFFHeXM1SjVGMzVXUWhNWGZkenJqdDhUS0pKc1ZQZTNyN0NYMnNhOUMvS3FSVEdjaU5oaUhmMllXU1NmcTA0Y0huSUZYMmRIVGVSOXh3ajY2dysiLCJtYWMiOiJlNjVhOWViYTZmNDI5M2E0MDIxYTVkMDU3NDA0MmU0YjJkOWM4M2RmZTMxOGJjZWMyNmNiYjg4YmFmNGU0NGM1IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:27:04 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlpXQlNBYXhUK2t2MkRzazdWUHFpeXc9PSIsInZhbHVlIjoiRnNuWUZmQ3BNbXFxQ1FIeWM3UWpLTERoZHZvTEFxTm1Ibk9VdXRhR3Rsa2tieFFHeXM1SjVGMzVXUWhNWGZkenJqdDhUS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im1pTUhpOTkzbjdhZTMxNzN1czk4eGc9PSIsInZhbHVlIjoianEzM0E1aHN6RnhyZ1ZkajFlanN1bU16WjFsajVpUmNEUVZ6dnNucmQyR1AvQ3hDSVo3czBDdXNmSnF3dERUWXJvd2RwUmhOSCt0R3pFa2piaXlrS2dPWkVxZWtYUldwaDVkdWdpMUZoRjlHUmp6UHptSXRRamZRQ3pkNkMyM0giLCJtYWMiOiI2YWMwZjI1MzNlOGMzNzE3ZTJkODI2MDhmMDBmN2UzMTdkMjhmNTgxMGRlYjAyZWI4OGRkODI3YTYwYTNjYWEzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Im1pTUhpOTkzbjdhZTMxNzN1czk4eGc9PSIsInZhbHVlIjoianEzM0E1aHN6RnhyZ1ZkajFlanN1bU16WjFsajVpUmNEUVZ6dnNucmQyR1AvQ3hDSVo3czBDdXN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlpXQlNBYXhUK2t2MkRzazdWUHFpeXc9PSIsInZhbHVlIjoiRnNuWUZmQ3BNbXFxQ1FIeWM3UWpLTERoZHZvTEFxTm1Ibk9VdXRhR3Rsa2tieFFHeXM1SjVGMzVXUWhNWGZkenJqdDhUS0pKc1ZQZTNyN0NYMnNhOUMvS3FSVEdjaU5oaUhmMllXU1NmcTA0Y0huSUZYMmRIVGVSOXh3ajY2dysiLCJtYWMiOiJlNjVhOWViYTZmNDI5M2E0MDIxYTVkMDU3NDA0MmU0YjJkOWM4M2RmZTMxOGJjZWMyNmNiYjg4YmFmNGU0NGM1IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:27:04 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlpXQlNBYXhUK2t2MkRzazdWUHFpeXc9PSIsInZhbHVlIjoiRnNuWUZmQ3BNbXFxQ1FIeWM3UWpLTERoZHZvTEFxTm1Ibk9VdXRhR3Rsa2tieFFHeXM1SjVGMzVXUWhNWGZkenJqdDhUS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im1pTUhpOTkzbjdhZTMxNzN1czk4eGc9PSIsInZhbHVlIjoianEzM0E1aHN6RnhyZ1ZkajFlanN1bU16WjFsajVpUmNEUVZ6dnNucmQyR1AvQ3hDSVo3czBDdXNmSnF3dERUWXJvd2RwUmhOSCt0R3pFa2piaXlrS2dPWkVxZWtYUldwaDVkdWdpMUZoRjlHUmp6UHptSXRRamZRQ3pkNkMyM0giLCJtYWMiOiI2YWMwZjI1MzNlOGMzNzE3ZTJkODI2MDhmMDBmN2UzMTdkMjhmNTgxMGRlYjAyZWI4OGRkODI3YTYwYTNjYWEzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Im1pTUhpOTkzbjdhZTMxNzN1czk4eGc9PSIsInZhbHVlIjoianEzM0E1aHN6RnhyZ1ZkajFlanN1bU16WjFsajVpUmNEUVZ6dnNucmQyR1AvQ3hDSVo3czBDdXN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "cFyY1ptoTRTn6ugovaPXjsaHiTYFuA7yzDRvlGi9" "uc_cart_id" => "5735bcf8085db1a8c3666e645f72668c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2276" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:27:04GET/chapter/22761121926