ANALYTICAL TOOLS: INHOUDSTABEL
1. INTRODUCTIE ................................................................................................................................................................. 6
2. GAS CHROMATOGRAFIE: Q ............................................................................................................................................. 6
3. ANALYSE VAN RESIDUELE SOLVENTEN ............................................................................................................................ 6
INTRO ................................................................................................................................................................................................ 6
RESIDUELE SOLVENTEN (PH.EUR) ............................................................................................................................................................ 6
GUIDELINES VOOR RS (CPMP/ICH/283/95) ........................................................................................................................................... 7
Intro ............................................................................................................................................................................................. 7
Kader ............................................................................................................................................................................................ 7
Algemene principes ...................................................................................................................................................................... 7
Analytische procedures.................................................................................................................................................................................. 7
Rapporteren levels (niveau) van RS ............................................................................................................................................................... 7
Limieten van RS ............................................................................................................................................................................ 8
Vermijdbare solventen................................................................................................................................................................................... 8
Solventen die gelimiteerd w .......................................................................................................................................................................... 8
Solventen met laag tox potentieel ................................................................................................................................................................. 8
Solventen waarvoor niet voldoende tox data gevonden ............................................................................................................................... 8
IDENTIFICATIE EN CONTROLE VAN RS ........................................................................................................................................................ 8
HEADSPACE ANALYSE: ........................................................................................................................................................................... 9
4. DUNNE LAAG CHROMATOGRAFIE: Q .............................................................................................................................. 9
5. TLC-RECENTE TOEPASSINGEN ......................................................................................................................................... 9
BESTRIJDEN VAN DE PLAAG VAN VERVALSTE GM ......................................................................................................................................... 9
BESCHERMING KINDEREN VAN PATULINE CONTAMINATIE IN APPELSAP ............................................................................................................. 9
ONDERZOEK H1N1 VACCIN .................................................................................................................................................................... 9
FORENSISCHE WETENSCHAP .................................................................................................................................................................... 9
6. TLC-MALDI .................................................................................................................................................................... 10
INTRO .............................................................................................................................................................................................. 10
Voordelen ................................................................................................................................................................................... 10
Nadelen ...................................................................................................................................................................................... 10
LC-MS vs TLC-MS ........................................................................................................................................................................ 10
MALDI-MS .................................................................................................................................................................................. 10
TOF-MS....................................................................................................................................................................................... 11
DETECTIE EN IDENTIFICATIE VAN VERWANTE STOFFEN/VERBINDINGEN ........................................................................................................... 11
Voorbeeld figuur 1 en 2 (GM + verwante verbinding product Pfizer) ........................................................................................ 11
Figuur 3: voordelen van deze set-up .......................................................................................................................................... 12
Post-source decay (PSD) ............................................................................................................................................................. 12
Figuur 4 ...................................................................................................................................................................................... 12
KWANTITATIEVE ASPECTEN ................................................................................................................................................................... 12
Voordelen ................................................................................................................................................................................... 12
Analyse van piroxicam (NSAID) .................................................................................................................................................. 12
CONCLUSIES ....................................................................................................................................................................................... 13
7. ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHY ............................................................................................ 13
INTRODUCTIE ..................................................................................................................................................................................... 13
High throughput ......................................................................................................................................................................... 13
Ontw snelle LC ............................................................................................................................................................................ 13
U-HPLC ......................................................................................................................................................................................................... 13
Monolytisch ................................................................................................................................................................................................. 14
Gebruik hoge kolom T’en (hoge temperatuur LC) ....................................................................................................................................... 14
CONCERNS ABOUT STABILITY EN DEGRADATIE ........................................................................................................................................... 14
Efficiëntie stijgt als partikels smaller w (sub-2µm) .................................................................................................................... 14
, Effiecientie en backpressure....................................................................................................................................................... 14
Toename in snelheid en scheiding.............................................................................................................................................. 14
Toegenomen druk daling ........................................................................................................................................................... 14
Fixed kolom efficientie ............................................................................................................................................................... 15
Wrijvingswarmte........................................................................................................................................................................ 15
Extra-kolom band verbreding .................................................................................................................................................... 15
Pakking materiaal: poreus vs. Niet poreuze deeltjes ................................................................................................................. 15
DETECTIE .......................................................................................................................................................................................... 16
METHODE TRANSFER ........................................................................................................................................................................... 16
Transfer van Ph.Eur. HPLC methode voor ibuprofen en gerelateerde stoffen nr U-HPLC .......................................................... 16
Industrie ..................................................................................................................................................................................... 16
CONCLUSIE: U-HPLC VS HPLC ............................................................................................................................................................. 16
8. HPLC: Q......................................................................................................................................................................... 16
9. NIEUWE ONTWIKKELINGEN IN SF.................................................................................................................................. 17
1. CORE-SHELL DEELTJES ............................................................................................................................................................... 17
Sub-2µm ..................................................................................................................................................................................... 17
Superficiele poreuze partikels .................................................................................................................................................... 17
CS deeltjes .................................................................................................................................................................................................... 17
2. 2DE GENERATIE MONOLYTEN ...................................................................................................................................................... 18
Twee grote categorieën: ............................................................................................................................................................ 18
Bv. Monolytische poly(styreen-divinylbenzeen) kolommen ........................................................................................................................ 18
Grootste verschil tss beide........................................................................................................................................................................... 18
Polymeer industrie ..................................................................................................................................................................... 18
Silica’s populariteit ..................................................................................................................................................................... 19
Monolyten niet vaak gebruikt? .................................................................................................................................................................... 19
3 nieuwe strategieën voor bereiding capillaire monolyten ........................................................................................................ 19
10. MS (ROZINSKI) .............................................................................................................................................................. 20
WAT IS DE MASSA VAN ATOMEN ............................................................................................................................................................ 20
Moleculaire massa ..................................................................................................................................................................... 20
INSTRUMENTATIE ............................................................................................................................................................................... 20
Ion bronnen ................................................................................................................................................................................ 20
Vacuum ........................................................................................................................................................................................................ 21
Elektronen ionisatie ................................................................................................................................................................................. 21
Chemische ionisatie ................................................................................................................................................................................. 21
MALDI....................................................................................................................................................................................................... 21
Atmosferische druk ...................................................................................................................................................................................... 22
Elektronen spray ...................................................................................................................................................................................... 22
APCI .......................................................................................................................................................................................................... 22
Analisator(en) ............................................................................................................................................................................ 23
Magnetische sector ...................................................................................................................................................................................... 23
Electrostatische analysator .......................................................................................................................................................................... 23
Dubbele focus MS .................................................................................................................................................................................... 23
Quadrupole .................................................................................................................................................................................................. 23
Ion trap......................................................................................................................................................................................................... 24
Orbitrap........................................................................................................................................................................................................ 24
Time of flight ................................................................................................................................................................................................ 24
Traveling wave ............................................................................................................................................................................................. 25
Ion mobiliteit................................................................................................................................................................................................ 25
Detector ..................................................................................................................................................................................... 25
Electron multiplier ....................................................................................................................................................................................... 25
Photon multiplier ......................................................................................................................................................................................... 25
Tandem ms................................................................................................................................................................................. 26
Als voorbeeld bespreken we de mogelijkheden van een triple quadrupole instrument ...................................................................... 26
product ionenscan .................................................................................................................................................................................. 26
voorloper ionenscan ............................................................................................................................................................................... 27
1. INTRODUCTIE ................................................................................................................................................................. 6
2. GAS CHROMATOGRAFIE: Q ............................................................................................................................................. 6
3. ANALYSE VAN RESIDUELE SOLVENTEN ............................................................................................................................ 6
INTRO ................................................................................................................................................................................................ 6
RESIDUELE SOLVENTEN (PH.EUR) ............................................................................................................................................................ 6
GUIDELINES VOOR RS (CPMP/ICH/283/95) ........................................................................................................................................... 7
Intro ............................................................................................................................................................................................. 7
Kader ............................................................................................................................................................................................ 7
Algemene principes ...................................................................................................................................................................... 7
Analytische procedures.................................................................................................................................................................................. 7
Rapporteren levels (niveau) van RS ............................................................................................................................................................... 7
Limieten van RS ............................................................................................................................................................................ 8
Vermijdbare solventen................................................................................................................................................................................... 8
Solventen die gelimiteerd w .......................................................................................................................................................................... 8
Solventen met laag tox potentieel ................................................................................................................................................................. 8
Solventen waarvoor niet voldoende tox data gevonden ............................................................................................................................... 8
IDENTIFICATIE EN CONTROLE VAN RS ........................................................................................................................................................ 8
HEADSPACE ANALYSE: ........................................................................................................................................................................... 9
4. DUNNE LAAG CHROMATOGRAFIE: Q .............................................................................................................................. 9
5. TLC-RECENTE TOEPASSINGEN ......................................................................................................................................... 9
BESTRIJDEN VAN DE PLAAG VAN VERVALSTE GM ......................................................................................................................................... 9
BESCHERMING KINDEREN VAN PATULINE CONTAMINATIE IN APPELSAP ............................................................................................................. 9
ONDERZOEK H1N1 VACCIN .................................................................................................................................................................... 9
FORENSISCHE WETENSCHAP .................................................................................................................................................................... 9
6. TLC-MALDI .................................................................................................................................................................... 10
INTRO .............................................................................................................................................................................................. 10
Voordelen ................................................................................................................................................................................... 10
Nadelen ...................................................................................................................................................................................... 10
LC-MS vs TLC-MS ........................................................................................................................................................................ 10
MALDI-MS .................................................................................................................................................................................. 10
TOF-MS....................................................................................................................................................................................... 11
DETECTIE EN IDENTIFICATIE VAN VERWANTE STOFFEN/VERBINDINGEN ........................................................................................................... 11
Voorbeeld figuur 1 en 2 (GM + verwante verbinding product Pfizer) ........................................................................................ 11
Figuur 3: voordelen van deze set-up .......................................................................................................................................... 12
Post-source decay (PSD) ............................................................................................................................................................. 12
Figuur 4 ...................................................................................................................................................................................... 12
KWANTITATIEVE ASPECTEN ................................................................................................................................................................... 12
Voordelen ................................................................................................................................................................................... 12
Analyse van piroxicam (NSAID) .................................................................................................................................................. 12
CONCLUSIES ....................................................................................................................................................................................... 13
7. ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHY ............................................................................................ 13
INTRODUCTIE ..................................................................................................................................................................................... 13
High throughput ......................................................................................................................................................................... 13
Ontw snelle LC ............................................................................................................................................................................ 13
U-HPLC ......................................................................................................................................................................................................... 13
Monolytisch ................................................................................................................................................................................................. 14
Gebruik hoge kolom T’en (hoge temperatuur LC) ....................................................................................................................................... 14
CONCERNS ABOUT STABILITY EN DEGRADATIE ........................................................................................................................................... 14
Efficiëntie stijgt als partikels smaller w (sub-2µm) .................................................................................................................... 14
, Effiecientie en backpressure....................................................................................................................................................... 14
Toename in snelheid en scheiding.............................................................................................................................................. 14
Toegenomen druk daling ........................................................................................................................................................... 14
Fixed kolom efficientie ............................................................................................................................................................... 15
Wrijvingswarmte........................................................................................................................................................................ 15
Extra-kolom band verbreding .................................................................................................................................................... 15
Pakking materiaal: poreus vs. Niet poreuze deeltjes ................................................................................................................. 15
DETECTIE .......................................................................................................................................................................................... 16
METHODE TRANSFER ........................................................................................................................................................................... 16
Transfer van Ph.Eur. HPLC methode voor ibuprofen en gerelateerde stoffen nr U-HPLC .......................................................... 16
Industrie ..................................................................................................................................................................................... 16
CONCLUSIE: U-HPLC VS HPLC ............................................................................................................................................................. 16
8. HPLC: Q......................................................................................................................................................................... 16
9. NIEUWE ONTWIKKELINGEN IN SF.................................................................................................................................. 17
1. CORE-SHELL DEELTJES ............................................................................................................................................................... 17
Sub-2µm ..................................................................................................................................................................................... 17
Superficiele poreuze partikels .................................................................................................................................................... 17
CS deeltjes .................................................................................................................................................................................................... 17
2. 2DE GENERATIE MONOLYTEN ...................................................................................................................................................... 18
Twee grote categorieën: ............................................................................................................................................................ 18
Bv. Monolytische poly(styreen-divinylbenzeen) kolommen ........................................................................................................................ 18
Grootste verschil tss beide........................................................................................................................................................................... 18
Polymeer industrie ..................................................................................................................................................................... 18
Silica’s populariteit ..................................................................................................................................................................... 19
Monolyten niet vaak gebruikt? .................................................................................................................................................................... 19
3 nieuwe strategieën voor bereiding capillaire monolyten ........................................................................................................ 19
10. MS (ROZINSKI) .............................................................................................................................................................. 20
WAT IS DE MASSA VAN ATOMEN ............................................................................................................................................................ 20
Moleculaire massa ..................................................................................................................................................................... 20
INSTRUMENTATIE ............................................................................................................................................................................... 20
Ion bronnen ................................................................................................................................................................................ 20
Vacuum ........................................................................................................................................................................................................ 21
Elektronen ionisatie ................................................................................................................................................................................. 21
Chemische ionisatie ................................................................................................................................................................................. 21
MALDI....................................................................................................................................................................................................... 21
Atmosferische druk ...................................................................................................................................................................................... 22
Elektronen spray ...................................................................................................................................................................................... 22
APCI .......................................................................................................................................................................................................... 22
Analisator(en) ............................................................................................................................................................................ 23
Magnetische sector ...................................................................................................................................................................................... 23
Electrostatische analysator .......................................................................................................................................................................... 23
Dubbele focus MS .................................................................................................................................................................................... 23
Quadrupole .................................................................................................................................................................................................. 23
Ion trap......................................................................................................................................................................................................... 24
Orbitrap........................................................................................................................................................................................................ 24
Time of flight ................................................................................................................................................................................................ 24
Traveling wave ............................................................................................................................................................................................. 25
Ion mobiliteit................................................................................................................................................................................................ 25
Detector ..................................................................................................................................................................................... 25
Electron multiplier ....................................................................................................................................................................................... 25
Photon multiplier ......................................................................................................................................................................................... 25
Tandem ms................................................................................................................................................................................. 26
Als voorbeeld bespreken we de mogelijkheden van een triple quadrupole instrument ...................................................................... 26
product ionenscan .................................................................................................................................................................................. 26
voorloper ionenscan ............................................................................................................................................................................... 27
