Umbhali / 1,2 Hu Rong 1 Hol igubu Igubu Ingoma Xuezhi phambi kokhenketho 1 Jinsong 1 – Entsha 1, 2
【Abstract】Iglasi yeBorosilicate sisixhobo sokupakisha esisetyenziswa kakhulu kunye nesingxobo sesisombululo kwishishini lamayeza.Nangona ineempawu zokuxhathisa okuphezulu, njengokugudiswa, ukumelana nokugqwala kunye nokunganyangeki, ii-ion zetsimbi kunye namaqela e-silanol aqulethwe kwiglasi ye-borosilicate isenokunxibelelana namachiza.Kuphononongo lwamachiza ekhemikhali ngolwelo oluphezulu lwechromatography (HPLC), ivial yenaliti eqhelekileyo yiglasi yeborosilicate.Ngokuphanda umphumo we-HPLC yeglasi yeglasi yeempawu ezintathu ekuzinzeni kwe-solifenacin succinate eyikhompawundi ye-alkaline ebuthathaka, kwafunyaniswa ukuba i-adsorption kumachiza e-alkaline ikhona kwiiglasi zeglasi eziveliswe ngabavelisi abahlukeneyo.I-adsorption yayibangelwa ikakhulu kukusebenzisana kwe-protonated amino kunye neqela le-dissociative silanol, kwaye ubukho be-succinate bakhuthaza.Ukongezwa kwe-hydrochloric acid kunokutshabalalisa ichiza okanye ukongeza umlinganiselo ofanelekileyo wezinyibilikisi eziphilayo kunokuthintela i-adsorption.Injongo yeli phepha kukukhumbuza amashishini ovavanyo lweziyobisi ukuba anikele ingqalelo kwintsebenziswano phakathi kwamachiza e-alkaline kunye neglasi, kunye nokunciphisa ukutenxa kwedatha kunye nomsebenzi wophando wokutenxa okubangelwa kukunqongophala kolwazi lweempawu ze-adsorption zeebhotile zeglasi kwi. inkqubo yohlalutyo lwamachiza.
Amagama aphambili: I-Solifenacin succinate, iqela le-amino, iiglasi zeglasi zeHPLC, i-adsorb
I-Glass njengento yokupakisha ineenzuzo zokulula, ukupheliswa okulula kunye nokumelana nokugqwala.I-Corrosion, ukumelana nokugqoka, ukuzinza kwevolumu kunye nezinye iingenelo, ngoko isetyenziswa ngokubanzi kwisicelo seyeza.Iglasi yonyango yohlulwe kwiglasi ye-sodium ye-calcium kunye neglasi ye-borosilicate, ngokwezinto ezahlukeneyo eziquletheyo.Phakathi kwazo, i-soda lime glass iqulethe i-71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;iglasi ye-borosilicate iqulethe i-70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O kunye ne-K2O kunye ne-2% ~ 4% Al2O3.Iglasi yeBorosilicate inokumelana nekhemikhali okugqwesileyo ngenxa yokusetyenziswa kweB2O3 endaweni yeninzi yeNa2O kunye neCaO.
Ngenxa yobume bayo benzululwazi, yakhethwa njengesona sikhongozeli siphambili seyeza elingamanzi.Nangona kunjalo, iglasi ye-boronSilicone, nokuba inganyangeki kakhulu, isenokunxibelelana namachiza, Zine iindlela zokusabela eziqhelekileyo ngolu hlobo lulandelayo [1]:
1) Utshintshiselwano lwe-Ion: Na +, K +, Ba2+, Ca2+ kwiglasi ye-ion exchange exchange kunye ne-H3O + kwisisombululo, kwaye kukho ukusabela phakathi kwee-ion ezitshintshiweyo kunye neziyobisi;
I-2) Ukuchithwa kweglasi: I-Phosphate, i-oxalate, i-Citrates kunye ne-tartrates iya kukhawulezisa ukuchithwa kweglasi kwaye ibangele i-silicides.kwaye i-Al3+ ikhutshwe kwisisombululo;
3) Ukonakala: I-EDTA ekhoyo kwisisombululo sechiza (EDTA) inokuba nzima kunye nee-ion ze-divalent okanye i-ion ze-trivalent kwiglasi.
4) I-Adsorption: Kukho ibhondi ye-Si-O eyaphukileyo kumphezulu weglasi, enokuthi ibhengeze i-H+
Ukwenziwa kwe-OH-kunokwenza iibhondi ze-hydrogen kunye namaqela athile kwichiza, okukhokelela ekubeni ichiza libhengezwe kumphezulu weglasi.
Uninzi lweekhemikhali ziqulethe amaqela e-amine abuthathaka, Xa kuhlalutywa amachiza ekhemikhali kunye ne-high performance liquid chromatography (HPLC), i-HPLC autosampler vial esetyenziswa ngokuqhelekileyo eyenziwe ngeglasi ye-borosilicate, kunye nobukho be-SiO- kumphezulu weglasi buya kusebenzisana neqela le-amine le-protonated. , ukuvumela ukuxinana kweziyobisi kuyancipha, iziphumo zokuhlalutya ziya kuba zingachanekanga, kunye ne-OOS yebhubhoratri (Ngaphandle kweNkcazo).Kule ngxelo, isiseko esibuthathaka (i-pKa yi-8.88[2]) ichiza le-solifenacin succinate (ifomula yolwakhiwo iboniswe kuMfanekiso 1) isetyenziswa njengento yophando, kunye nefuthe leebhotile ezininzi ze-amber borosilicate inaliti yeglasi kwimarike kuhlalutyo lweziyobisi. kuyaphandwa., kunye nombono wohlalutyo lokufumana isisombululo kwi-adsorption yamachiza anjalo kwiglasi.
1.Inxalenye yovavanyo
1.1Izixhobo kunye nezixhobo zovavanyo
1.1.1 Izixhobo: Ubuchule obuPhezulu obuPhezulu kunye ne-UV detector
Ichromatography yolwelo
1.1.2 Imathiriyeli yovavanyo: I-Solifenacin succinate API yaveliswa ngu-Alembic
Pharmaceuticals Ltd. (Indiya).Umgangatho we-Solifenacin (i-99.9% yococeko) yathengwa kwi-USP.I-ARgrade potassium dihydrogen phosphate, triethylamine, kunye ne-phosphoric acid zathengwa kwi-China Xilong Technology Co., Ltd. I-Methanol kunye ne-acetonitrile (zombini ibakala le-HPLC) zathengwa kwi-Sibaiquan Chemical Co., Ltd. Iibhotile ze-Polypropylene (PP) zathengwa kwi-ThermoScientific (US) , kunye ne-2ml amber HPLC iibhotile zeglasi zathengwa kwi-Agilent Technologies (China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., kunye neZhejiang Hamag Technology Co., Ltd. (A, B, C zisetyenziswa ngezantsi ukumela imithombo eyahlukeneyo yeglasi yeglasi, ngokulandelanayo).
1.2Indlela yokuhlalutya yeHPLC
1.2.1I-Solifenacin succinate kunye ne-solifenacin isiseko samahhala: ikholamu yechromatographic isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3 µm.Nge-phosphate buffer (ubunzima be-4.1 g ye-potassium dihydrogen phosphate, ubunzima be-2 ml ye-triethylamine, yongeza kwi-1 L yamanzi e-ultrapure, xuba ukunyibilika, usephosphoric acid (pH yahlengahlengiswa kwi-2.5) -acetonitrile-methanol (40:30:30) njengenqanaba elihambayo,
Umzobo 1 Ifomula yesakhiwo solifenacin succinate
Umzobo 2 Ukuthelekiswa kweendawo eziphakamileyo zesisombululo esifanayo se-solifenacin succinate kwiibhotile zePP kunye neeglasi ezivela kubavelisi abathathu A, B, kunye noC.
izinga lokushisa kwekholomu laliyi-30 ° C, izinga lokuhamba laliyi-1.0 mL / min, kwaye umthamo we-injection wawuyi-50 mL, i-wavelength yokufumanisa yi-220 nm.
1.2.2 Isampulu ye-Succinic acid: usebenzisa i-YMC-PACK ODS-A 4.6 mm × 150 mm, ikholamu ye-3 µm, 0.03 mol/L i-phosphate buffer (elungelelaniswe kwi-pH 3.2 nge-asidi ye-phosphoric) -methanol (92:8) njengesigaba esihambayo, ukuhamba izinga le-1.0 mL / min, ubushushu bekholomu yi-55 ° C, kunye nomthamo we-injection ngu-90 mL.I-Chromatograms yafunyanwa kwi-204 nm.
1.3 Indlela yohlalutyo ye-ICP-MS
Izinto ezikwisisombululo zahlaziywa kusetyenziswa inkqubo ye-Agilent 7800 ICP-MS, imowudi yokuhlalutya yayiyi-He mode (4.3mL / min), amandla e-RF yi-1550W, i-plasma gasflow rate yayiyi-15L / min, kunye nesantya sokuhamba kwegesi ye-carrier ibiyi-1.07mL/min.Iqondo lokushisa kwegumbi lenkungu laliyi-2 ° C, i-peristaltic pump lifting / stabilizing speed yi-0.3 / 0.1 rps, ixesha lokuzinzisa isampula laliyi-35 s, ixesha lokuphakamisa isampuli laliyi-45 s, kunye nobunzulu bokuqokelela buyi-8 mm.
Ukulungiselela isampuli
I-Solifenacin isisombululo se-succinate: ilungiselelwe ngamanzi a-ultrapur, i-concentration yi-0.011 mg / mL.
1.4.2 Isisombululo se-Succinic acid: ilungiswe ngamanzi e-ultrapure, i-concentration yi-1mg / mL.
I-1.4.3 isisombululo se-Solifenacin: ukuchithwa kwe-solifenacin i-succinate emanzini, i-sodium carbonate yongezwa, kwaye emva kokuba isisombululo sitshintshile kwi-tomilky emhlophe engenambala, i-ethyl acetate yongezwa.I-ethyl acetate layer yahlulwa kwaye i-solvent yakhutshwa ngumphunga ukunika i-solifenacin.Ukunyibilikisa isixa esifanelekileyo se-solifenacin inethanol (i-ethanol i-akhawunti ye-m 5% kwisisombululo sokugqibela), kwaye emva koko uhlambulule ngamanzi ukuze ulungiselele isisombululo kunye ne-concentration ye-0.008 mg/mL solifenacin (kunye ne-solifenacin isisombululo se-succinate equlethwe kwisisombululo esifanayo ne-solifenacin ugxininiso).
Iziphumo neengxoxo
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2.1 Umthamo we-Adsorption wee-vials ze-HPLC zeempawu ezahlukeneyo
Ukhupha isisombululo esifanayo se-aqueous se-solifenacin succinate kwii-PP ii-vials kunye ne-3 brand ye-autosampler vials zaye zatofwa ngamaxesha athile kwindawo efanayo, kwaye indawo ephakamileyo yencopho ephambili yarekhodwa.Ukususela kwiziphumo kwi-Figure 2, kunokubonwa ukuba indawo ephezulu ye-PP izinzile, kwaye akukho phantse utshintsho emva kwe-44 h. Ngelixa iindawo eziphakamileyo zeempawu ezintathu zeglasi zeglasi kwi-0 h zazincinci kunebhotile ye-PP. , kwaye indawo ephakamileyo iyaqhubeka iyancipha ngexesha lokugcinwa.
Umzobo 3 Utshintsho kwiindawo eziphakamileyo ze-solifenacin, i-succinic acid, kunye ne-solifenacin i-succinate isisombululo se-aqueous egcinwe kwiiglasi zeglasi kunye ne-PP.
Ukuqhubela phambili ukufunda le nto, i-solifenacin, i-asidi ye-succinate, izisombululo ze-Aqueous ze-solifenacin acid kunye ne-succinate kwiibhotile zeglasi zomenzi we-Band PP iibhotile ukuphanda utshintsho lwendawo ephezulu ngexesha, kwaye kwangaxeshanye iglasi.
Izisombululo ezithathu kwiibhotile zaye zadityaniswa kusetyenziswa i-Agilent 7800 ICP-MSPlasma mass spectrometer yohlalutyo olusisiseko.Idatha ekuMfanekiso 3 ibonisa ukuba iibhotile zeglasi kwindawo enamanzi azizange zifake i-asidi ye-succinic, kodwa i-adsorbed solifenacinFree base kunye ne-solifenacin succinate.Iingqayi zeglasi zidsorb succinate.Ubungakanani be-linacin bomelele kunobo be-solifenacin isiseko sasimahla, ngexesha lokuqala i-Solifenacin succinate kunye ne-solifenacin isiseko sasimahla kwiibhotile zeglasi.Imilinganiselo yeendawo eziphakamileyo zezisombululo eziqulethwe kwiibhotile ze-PP ziyi-0.94 kunye ne-0.98, ngokulandelanayo.
Ngokuqhelekileyo kukholelwa ukuba umphezulu weglasi ye-silicate inokufunxa amanzi athile, athi amanye amanzi adibanise ne-Si4 + ngendlela yamaqela e-OH ukwenza amaqela e-silanol Ekubunjweni kweglasi ye-oxide, i-ion ze-polyvalent azikwazi ukuhamba, kodwa isinyithi se-alkali (ezifana ne I-Na + ) kunye ne-alkaline yomhlaba i-ion zetsimbi (ezifana ne-Ca2 +) zinokuhamba xa iimeko zivuma, ngokukodwa ii-ion zetsimbi ze-alkali zihamba ngokulula, zinokutshintshiselana nge-H + i-adsorbed kwi-glass surface andTransfer kumphezulu weglasi ukwenza amaqela e-silanol [3-4].Ke ngoko, uxinzelelo lwe-H + lokunyuka kunokukhuthaza utshintshiselwano lwe-ion ukunyusa amaqela e-silanol kumphezulu weglasi.nge table1 ibonisa ukuba umxholo we B, Na, kunye no Ca kwisisombululo uyahluka ukusuka phezulu ukuya phantsi.zi-asidi ye-succinic, i-solifenacin succinate kunye ne-solifenacin.
isampulu B (μg/L) Na(μg/L) Ca(μg/L) Al(μg/L) Si(μg/L) Fe(μg/L)
amanzi 2150 3260 20 Akukho Ukufunyanwa 1280 4520
Isisombululo seSuccinic acid 3380 5570 400 429 1450 139720
ISolifenacin Succinate Solution 2656 5130 380 Akukho Ukufunyanwa 2250 2010
isisombululo solifenacin 1834 2860 200 Akukho ukufunyanwa 2460 Akukho kufunyanwa
Itheyibhile 1 Ugxininiso lwe-Elemental ye-solifenacin succinate, i-solifenacin kunye ne-succinic acid isisombululo se-aqueous esigcinwe kwiiglasi zeglasi iintsuku ezi-8
Ukongezelela, kunokubonwa kwidatha kwiThebhile 2 ukuba emva kokugcinwa kwiibhotile zeglasi kwi-24 h, i-dissolved I-pH ye-liquid ivukile.Lo mcimbi usondele kakhulu kule thiyori ingentla
Inombolo yeVial yoBuyiselo emva kokugcinwa kwiglasi ye-71 h
(%) Izinga lokubuyisela emva kokulungiswa kwe-PH
IVial 1 97.07 100.35
IVial 2 98.03 100.87
IVial 3 87.98 101.12
IVial 4 96.96 100.82
IVial 5 98.86 100.57
IVial 6 92.52 100.88
IVial 7 96.97 100.76
IVial 8 98.22 101.37
IVial 9 97.78 101.31
Itheyibhile 3 Imeko yokuchithwa kwe-solifenacin succinate emva kokudityaniswa kweasidi
Ekubeni i-Si-OH kumphezulu weglasi inokudityaniswa ibe yi-SiO-[5] phakathi kwe-pH 2 ~ 12, ngelixa i-solifenacin yenzeka i-N kwindawo ene-acidic Protonation (ilinganiswe pH yesisombululo se-aqueous ye-solifenacin succinate yi-5.34, ixabiso le-pH le-solifenacin isisombululo ngu-5.80), kwaye umahluko phakathi kwentsebenziswano emibini ye-Hydrophilic ikhokelela ekubhengezeni iziyobisi kwiglasi (Umfanekiso we-3), i-solifenacin yabhengezwa ngakumbi nangakumbi ngokuhamba kwexesha.
Ukongeza, iBacon kunye neRaggon [6] yafumanisa ukuba kwisisombululo esingathathi hlangothi, i-hydroxy acids eneqela le-hydroxyl kwindawo ehambelana neqela le-carboxyl Izisombululo zetyuwa zinokukhupha i-silicion ene-oxidized.Kwisakhiwo semolekyuli ye-solifenacin succinate, kukho iqela le-hydroxyl ngokumalunga nendawo ye-carboxylate, eya kuhlasela kwiglasi, i-SiO2 ikhutshwe kwaye iglasi iyakhukuliswa.Ngoko ke, emva kokubunjwa kwetyuwa kunye ne-succinic acid, i-adsorption ye-solifenacin emanzini ibonakala ngakumbi.
2.2 Iindlela zokuthintela i-adsorption
Ixesha lokugcina pH
0h 5.50
24h 6.29
48h 6.24
Uluhlu lwe-2 pH utshintsho lwezisombululo ezinamanzi ze-solifenacin succinate kwiibhotile zeglasi
Nangona iibhotile zePP zingabhengezi i-solifenacin succinate, Kodwa ngexesha lokugcinwa kwesisombululo kwi-PP vial, ezinye iincopho zokungcola ziveliswa kwaye Ukwandiswa kwexesha lokugcina ngokuthe ngcembe kwandisa indawo yokungcola, okubangele ukuphazamiseka ekubonweni kweyona ndawo iphakamileyo. .
Ngoko ke, kuyimfuneko ukuhlola indlela enokuthintela i-glass adsorption.
Thatha i-1.5 mL ye-solifenacin succinate isisombululo esimanzi kwi-vial yeglasi.Emva kokufakwa kwisisombululo se-71 h, amazinga okubuyisela ayephantsi.Yongeza i-0.1M i-hydrochloric acid, lungisa i-pH malunga ne-2.3, ukusuka kwidatha kwiThebhile 3. Ingabonwa ukuba amazinga okubuyisela onke abuyele kumanqanaba aqhelekileyo, ebonisa ukuba ukusabela kwexesha lokugcinwa kwe-adsorption kunokuvinjelwa kwi-pH ephantsi.
Enye indlela kukunciphisa i-adsorption ngokongeza izinyibilikisi eziphilayo.Yenza i-10%, i-20%, i-30%, i-50% ye-methanol, i-ethanol, i-isopropanol, i-acetonitrile yalungiselelwa kwi-concentration ye-0.01 mg / mL kwi-Solifenacin succinate liquid.Ezi zisombululo zingentla zafakwa kwiibhotile zeglasi kunye neebhotile zePP, ngokulandelelanayo.Kwiqondo lobushushu begumbi Ukuzinza kwayo kwafundwa imiboniso.Uphando lufumanise ukuba isinyibilikisi esincinci kakhulu asikwazi ukuthintela i-adsorption, ngelixa isinyibilikisi se-organic esininzi kakhulu siya kukhokelela kwincopho engaqhelekanga yokumila kwencochoyi enkulu ngenxa yesiphumo sokunyibilikisa.Kuphela izinyibilikisi eziphilayo eziphakathi kuphela zinokongezwa ukuthintela ngempumelelo i-succinic acid I-Solifenacin ifakwe kwiglasi, yongeza i-50% ye-methanol okanye i-ethanol okanye i-30% ~ 50% ye-acetonitrile inokoyisa intsebenziswano ebuthathaka phakathi kwechiza kunye nomphezulu we-vial.
Iingqayi zePP zeglasi Iingqayi zeglasi
Ixesha lokugcina 0h 0h 9.5h 17h 48h
30% iacetonitrile 823.6 822.5 822 822.6 823.6
50% acetonitrile 822.1 826.6 828.9 830.9 838.5
30% isopropanol 829.2 823.1 821.2 820 806.9
50% ethanol 828.6 825.6 831.4 832.7 830.4
50% imethanol 835.8 825 825.6 825.8 823.1
Itheyibhile 4 Iziphumo zezinyibilikisi ezahlukeneyo zendalo kwi-adsorption yeebhotile zeglasi
ukuba i-solifenacin succinate igcinwa ngokukhethwa kwisisombululo.Uluhlu 4 amanani
Kuye kwaboniswa ukuba xa i-solifenacin succinate igcinwe kwiglasi yeglasi, sebenzisa
Emva kokuba isisombululo se-organic solvent salo mzekelo ungasentla sihlanjululwe, i-succinate kwiiglasi zeglasi.Ummandla ophakamileyo we-linacin ngaphakathi kwe-48h iyafana nendawo ephakamileyo ye-PP vial kwi-0h.Phakathi kwe-0.98 kunye ne-1.02, idatha izinzile.
3.0 isiphelo:
Iimpawu ezahlukeneyo zeglasi zeglasi zesiseko esibuthathaka sekhompawundi i-succinic acid Solifenacin iya kuvelisa amanqanaba ahlukeneyo e-adsorption, i-adsorption ibangelwa ikakhulu kukunxibelelana kwamaqela e-amine aneprotonated kunye namaqela e-silanol asimahla.Ke ngoko, eli nqaku likhumbuza iinkampani zovavanyo lwamachiza ukuba ngexesha lokugcina ulwelo okanye uhlalutyo, qiniseka ukuba unikel' ingqalelo ekulahlekeni kwechiza, i-pH efanelekileyo ediluent okanye i-pH efanelekileyo ediluent inokuphandwa kwangaphambili.Umzekelo ke kwizinyibilikisi ze-oganic ukuphepha ukusebenzisana phakathi kwamachiza asisiseko kunye neglasi, ukuze kuncitshiswe ukuthambekela kwedatha ngexesha lohlalutyo lwamachiza kunye nesiphumo sokuthambekela kuphando.
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Umzobo 4. Ukusebenzisana phakathi kweqela le-protonated amino ye-solifenacin kunye namaqela e-silanol adityanisiweyo kumphezulu weglasi.
Ixesha lokuposa: May-26-2022