Wolemba / 1,2 Hu Rong 1 Hol ng'oma Drum Song Xuezhi pamaso pa ulendo umodzi wa Jinsong 1 - Watsopano 1, 2
【Abstract】 Galasi ya Borosilicate ndi chida chomwe chimagwiritsidwa ntchito kwambiri pakuyika ndi yankho pamakampani opanga mankhwala.Ngakhale ali ndi zizindikiro zotsutsa kwambiri, monga zosalala, kukana kwa dzimbiri ndi kukana kuvala, zitsulo zazitsulo ndi magulu a silanol omwe ali mu galasi la borosilicate akhoza kuyanjanabe ndi mankhwala.Pakuwunika kwamankhwala amankhwala pogwiritsa ntchito high performance liquid chromatography (HPLC), jekeseni wamba ndi galasi la borosilicate.Pofufuza zotsatira za HPLC galasi Mbale za zopangidwa atatu pa kukhazikika kwa solifenacin succinate amene ndi ofooka zamchere pawiri, anapeza kuti adsorption kwa mankhwala amchere analipo mu galasi Mbale opangidwa ndi opanga osiyanasiyana.Kutsatsaku kudachitika makamaka chifukwa cha kuyanjana kwa gulu la protonated amino ndi dissociative silanol, ndipo kupezeka kwa succinate kunalimbikitsa.Kuphatikizika kwa hydrochloric acid kumatha kuwononga mankhwalawa kapena kuwonjezera gawo loyenera la zosungunulira za organic kungalepheretse kudsorption.Cholinga cha pepalali ndikukumbutsa mabizinesi oyezetsa mankhwala kuti azisamalira kulumikizana pakati pa mankhwala amchere ndi magalasi, komanso kuchepetsa kusokonekera kwa data ndi ntchito yofufuza yopatuka chifukwa cha kusowa kwa chidziwitso cha mawonekedwe a adsorption a mabotolo agalasi mu. ndondomeko ya kusanthula mankhwala.
Mawu ofunika: Solifenacin succinate, amino gulu, HPLC galasi Mbale, adsorb
Galasi ngati zinthu zonyamula katundu ali ndi ubwino wosalala, kuchotsa mosavuta ndi dzimbiri resistance.Corrosion, kuvala kukana, kukhazikika kwa voliyumu ndi ubwino wina, choncho amagwiritsidwa ntchito kwambiri popanga mankhwala.Galasi yamankhwala imagawidwa kukhala galasi la sodium calcium ndi galasi la borosilicate, malinga ndi magawo osiyanasiyana omwe ali nawo.Pakati pawo, koloko laimu galasi lili 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;galasi borosilicate lili 70%~80% SiO2, 7%~13%B2O3, 4%~6% Na2O ndi K2O ndi 2%~4% Al2O3.Magalasi a Borosilicate ali ndi mphamvu yolimbana ndi mankhwala chifukwa chogwiritsa ntchito B2O3 m'malo mwa Na2O ndi CaO ambiri.
Chifukwa cha chikhalidwe chake chasayansi, idasankhidwa kukhala chidebe chachikulu chamankhwala amadzimadzi.Komabe, galasi la boronSilicone, ngakhale litakana kwambiri, limatha kuyanjana ndi mankhwala, Pali njira zinayi zomwe zimachitikira motere [1]:
1) Kusinthana kwa ion: Na+, K+, Ba2+, Ca2+ mu galasi amalowetsamo ion kusinthana ndi H3O+ mu yankho, ndipo pali zomwe zimachitika pakati pa ma ion osinthanitsa ndi mankhwala;
2) Kusungunuka kwa galasi: Phosphate, oxalate, Citrates ndi tartrates zidzafulumizitsa kusungunuka kwa galasi ndikuyambitsa ma silicides.ndipo Al3 + imamasulidwa kukhala yankho;
3) Kuwonongeka: EDTA yomwe ilipo mu njira yothetsera mankhwala (EDTA) ikhoza kukhala yovuta ndi ma ion a divalent kapena ma ion atatu mugalasi.
4) Adsorption: Pali chomangira chosweka cha Si-O pagalasi, chomwe chimatha kutsatsa H +
Mapangidwe a OH-akhoza kupanga ma hydrogen bond ndi magulu ena a mankhwalawa, zomwe zimapangitsa kuti mankhwalawa apangidwe pamwamba pa galasi.
Mankhwala ambiri amakhala ndi magulu ofooka a amine, Pofufuza mankhwala omwe ali ndi high performance liquid chromatography (HPLC), HPLC autosampler vial yomwe imagwiritsidwa ntchito ndi galasi la borosilicate, ndipo kukhalapo kwa SiO-pa galasi kumalumikizana ndi gulu la protonated amine. , kulola kuti kachulukidwe ka mankhwala achepetse, zotsatira za kusanthula zidzakhala zolakwika, ndi labotale OOS (Out of Specification).Mu lipotili, zofooka zoyamba (pKa ndi 8.88[2]) mankhwala solifenacin succinate (chilinganizo chopangidwa chikuwonetsedwa pa Chithunzi 1) chimagwiritsidwa ntchito ngati chinthu chofufuzira, komanso mphamvu ya mbale zingapo zamagalasi a amber borosilicate jekeseni pamsika pakuwunika mankhwala. akufufuzidwa., komanso kuchokera kuzinthu zowunikira kuti mupeze njira yothetsera kutengeka kwa mankhwalawa pagalasi.
1.Mayeso gawo
1.1Zida ndi zida zoyesera
1.1.1 Zida: Agilent High Kuchita bwino ndi UV Detector
Chromatography yamadzimadzi
1.1.2 Zida zoyesera: Solifenacin succinate API inapangidwa ndi Alembic
Pharmaceuticals Ltd. (India).Muyezo wa Solifenacin (99.9% chiyero) unagulidwa kuchokera ku USP.ARgrade potassium dihydrogen phosphate, triethylamine, ndi phosphoric acid anagulidwa kuchokera ku China Xilong Technology Co., Ltd. Methanol ndi acetonitrile (onse kalasi ya HPLC) anagulidwa kuchokera ku mabotolo a Sibaiquan Chemical Co., Ltd. Polypropylene (PP) anagulidwa kuchokera ku ThermoScientific (US) , ndi mabotolo agalasi a 2ml amber HPLC adagulidwa ku Agilent Technologies(China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., ndi Zhejiang Hamag Technology Co., Ltd. (A, B, C amagwiritsidwa ntchito pansipa kuyimira magwero osiyanasiyana a mbale zagalasi, motsatana).
1.2HPLC njira yowunikira
1.2.1Solifenacin succinate and solifenacin free base: the chromatographic column isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3 µm.Ndi phosphate buffer (kulemera 4.1 g wa potaziyamu dihydrogen mankwala, kulemera 2 ml ya triethylamine, kuwonjezera pa 1 L madzi ultrapure, kusonkhezera kupasuka, usephosphoric acid (pH anasinthidwa 2.5) -acetonitrile-methanol (40:30:30) monga gawo la mafoni,
Chithunzi 1 Structural formula of solifenacin succinate
Chithunzi 2 Kuyerekeza madera apamwamba a yankho lomwelo la solifenacin succinate mu PP Mbale ndi magalasi kuchokera kwa opanga atatu A, B, ndi C
kutentha kwa mzati kunali 30 ° C, kuthamanga kwake kunali 1.0 mL / min, ndipo voliyumu ya jekeseni inali 50 mL, kutalika kwa mawonekedwe ndi 220 nm.
1.2.2 Succinic acid chitsanzo: pogwiritsa ntchito YMC-PACK ODS-A 4.6 mm × 150 mm, 3 µm column, 0.03 mol/L phosphate buffer (yosinthidwa kukhala pH 3.2 withphosphoric acid) -methanol (92:8) monga gawo loyenda, kuyenda mlingo 1.0 mL/mphindi, mzati kutentha 55 °C, ndi voliyumu jakisoni anali 90 mL.Chromatograms adagulidwa pa 204 nm.
1.3 Njira yowunikira ya ICP-MS
Zomwe zili mu yankholo zidawunikidwa pogwiritsa ntchito Agilent 7800 ICP-MS system, njira yowunikira inali He mode (4.3mL/min), mphamvu ya RF inali 1550W, kuchuluka kwa gasflow ya plasma kunali 15L/min, ndi kuchuluka kwa gasi wonyamula. anali 1.07mL/mphindi.Kutentha kwa chipinda cha chifunga kunali 2 ° C, kuthamanga kwa pampu ya peristaltic / kukhazikika kunali 0.3 / 0.1 rps, nthawi yokhazikika yachitsanzo inali 35 s, nthawi yokweza chitsanzo inali 45 s, ndipo kuya kwake kunali 8 mm.
Kukonzekera kwachitsanzo
Solifenacin succinate solution: yokonzedwa ndi madzi a ultrapure, ndende yake ndi 0.011 mg/mL.
1.4.2 Succinic acid solution: yokonzedwa ndi madzi a ultrapure, ndende yake ndi 1mg/mL.
1.4.3 Solifenacin solution: Succinate solifenacin succinate m'madzi, sodium carbonate inawonjezeredwa, ndipo yankho litatha kusintha kuchokera ku tomilky white, ethyl acetate inawonjezeredwa.The ethyl acetate wosanjikiza analekanitsidwa ndipo thesolvent anaphwetsedwa nthunzi kupereka solifenacin.Sungunulani mlingo woyenerera wa solifenacin inethanol (ethanol ndi mamita 5% mu njira yomaliza), ndiyeno sungunulani ndi madzi kuti mukonzekere njira yothetsera 0,008 mg/mL solifenacin (ndi solifenacin succinate solution yomwe ili mu njira yofanana ndi solifenacin). kuganizira).
Zotsatira ndi zokambirana
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2.1 Kuchuluka kwa Adsorption kwa Mbale za HPLC zamitundu yosiyanasiyana
Perekani njira yamadzi yofananira ya solifenacin succinate mu PP Mbale ndi 3 zopangidwa za autosampler Mbale anabayidwa pa intervals mu malo omwewo, ndipo dera pachimake cha pachimake chachikulu chinalembedwa.Kuchokera pazotsatira mu Chithunzi 2, zikhoza kuwoneka kuti malo apamwamba a PP ndi okhazikika, ndipo palibe pafupifupi kusintha pambuyo pa 44 h. , ndipo malo apamwamba akupitirizabe kuchepa panthawi yosungirako.
Chithunzi 3 Kusintha kwa madera apamwamba kwambiri a solifenacin, succinic acid, ndi solifenacin succinate solutions amadzimadzi zosungidwa mu mbale zagalasi ndi PP.
Kuti mupitirize kuphunzira chodabwitsa ichi, solifenacin, asidi succinate, Amadzimadzi njira za asidi solifenacin ndi succinate mu galasi Mbale wopanga Band PP mabotolo kufufuza kusintha kwa pachimake dera ndi nthawi, ndi nthawi yomweyo galasi.
Mayankho atatu m'mabotolo adaphatikizidwa mothandizidwa ndi Agilent 7800 ICP-MSPlasma mass spectrometer pakuwunika koyambira.Zomwe zili mu Chithunzi 3 zikuwonetsa kuti Mbale za Glass mu sing'anga yamadzi sizimatsatsa succinic acid, koma zidatsitsa solifenacinFree base ndi solifenacin succinate.Magalasi Mbale adsorb succinate.Kukula kwa linacin ndi kolimba kuposa tsinde laulere la solifenacin, panthawi yoyamba Solifenacin succinate ndi solifenacin free base mu mbale zagalasi.Magawo a nsonga za mayankho omwe ali m'mabotolo a PP anali 0.94 ndi 0.98, motsatana.
Amakhulupirira kuti pamwamba pa galasi silicate amatha kuyamwa madzi ena, omwe madzi ena amaphatikizana ndi Si4 + mu mawonekedwe a magulu a OH kuti apange magulu a silanol Mu kapangidwe ka galasi la oxide, ayoni a polyvalent sangathe kusuntha, koma zitsulo zamchere (monga Na + ) ndi ayoni zamchere zamchere zamchere (monga Ca2 +) zimatha kusuntha ngati zinthu zilola, makamaka ayoni zitsulo zamchere ndizosavuta kutulutsa, zimatha kusinthana ndi H + adsorbed pagalasi pamwamba ndikusamutsira pamwamba pagalasi kupanga magulu a silanol [3-4].Chifukwa chake, kuchuluka kwa H +kukuwonjezeka kumatha kulimbikitsa kusinthana kwa ion kuti muwonjezere magulu a silanol pagalasi.ndi table1 ikuwonetsa kuti zomwe zili mu B, Na, ndi Ca mu yankho zimasiyanasiyana kuchokera kumtunda mpaka kutsika.ndi succinic acid, solifenacin succinate ndi solifenacin.
chitsanzo B (μg/L) Na(μg/L) Ca(μg/L) Al(μg/L) Si(μg/L) Fe(μg/L)
madzi 2150 3260 20 Palibe Kuzindikira 1280 4520
Succinic acid solution 3380 5570 400 429 1450 139720
Solifenacin Succinate Solution 2656 5130 380 Palibe Kuzindikira 2250 2010
solifenacin yankho 1834 2860 200 Palibe Kuzindikira 2460 Palibe Kuzindikira
Table 1 Kuchuluka kwa solifenacin succinate, solifenacin ndi succinic acid yamadzimadzi yosungidwa mu mbale zagalasi kwa masiku 8.
Kuonjezera apo, zikhoza kuwoneka kuchokera ku deta mu Table 2 kuti mutatha kusungidwa m'mabotolo agalasi kwa maola 24, kusungunuka pH yamadzimadzi yawuka.Chochitika ichi chiri pafupi kwambiri ndi chiphunzitso pamwambapa
Vial No. Kubwezeretsa mlingo pambuyo posungira mu galasi kwa 71 h
(%) Mulingo wochira pambuyo pa kusintha kwa PH
Mbale 1 97.07 100.35
Vial 2 98.03 100.87
Vial 3 87.98 101.12
Vial 4 96.96 100.82
Vial 5 98.86 100.57
Vial 6 92.52 100.88
Vial 7 96.97 100.76
Vial 8 98.22 101.37
Vial 9 97.78 101.31
Table 3 Desorption mkhalidwe wa solifenacin succinate pambuyo asidi kuwonjezera
Popeza Si-OH pa galasi pamwamba akhoza dissociated mu SiO--[5] pakati pH 2 ~ 12, pamene solifenacin amapezeka N mu malo acidic Protonation (kuyezedwa pH wa amadzimadzi njira ya solifenacin succinate ndi 5.34, pH mtengo wa solifenacin yankho ndi 5.80), ndipo kusiyana awiri Hydrophilic ankachita kumabweretsa mankhwala adsorption pa galasi pamwamba (mkuyu. 3), solifenacin anali adsorbed kwambiri ndi nthawi.
Kuphatikiza apo, Bacon ndi Raggon [6] adapezanso kuti munjira yosalowerera ndale, ma hydroxy acid okhala ndi gulu la hydroxyl pamalo okhudzana ndi gulu la carboxyl Mayankho amchere amatha kutulutsa silicon oxidized.Mu maselo a solifenacin succinate, pali gulu la hydroxyl logwirizana ndi malo a carboxylate, lomwe lidzaukira pa galasi, SiO2 imachotsedwa ndipo galasi imakokoloka.Chifukwa chake, pambuyo pakupanga mchere ndi succinic acid, kuyamwa kwa solifenacin m'madzi kumawonekeranso.
2.2 Njira zopewera kutsatsa
Nthawi yosungira pH
0h 5.50
24h 6.29
48h 6.24
Table 2 pH kusintha kwa amadzimadzi zothetsera solifenacin succinate mu galasi mabotolo
Ngakhale PP Mbale si adsorb solifenacin succinate, Koma pa kusungirako njira mu PP vial, zina zonyansa nsonga kwaiye ndi The kutalikitsa nthawi yosungirako pang`onopang`ono kuonjezera zonyansa pachimake m`dera, zomwe zinayambitsa kusokoneza kudziwika kwa pachimake chachikulu. .
Choncho, m'pofunika kufufuza njira yomwe ingalepheretse magalasi adsorption.
Tengani 1.5 ml ya solifenacin succinate amadzimadzi njira mu galasi galasi.Pambuyo poyikidwa mu njira yothetsera 71 h, ziwongola dzanja zonse zinali zotsika.Onjezani 0.1M hydrochloric acid, sinthani pH mpaka pafupifupi 2.3, kuchokera ku deta yomwe ili mu Table 3. Zitha kuwoneka kuti ziwongola dzanja zonse zimabwerera kumagulu abwino, zomwe zimasonyeza kuti nthawi yosungiramo adsorption ikhoza kuletsedwa pa pH yochepa.
Njira ina ndikuchepetsa kutsatsa powonjezera ma organic solvents.Pangani 10%, 20%, 30%, 50% methanol, Mowa, isopropanol, acetonitrile unakonzedwa pa ndende ya 0,01 mg/mL mu Solifenacin succinate madzi.Zomwe zili pamwambazi zidayikidwa mu mbale zagalasi ndi PP, motsatana.Pa kutentha kwa chipinda Kukhazikika kwake kunaphunziridwa ziwonetsero.Kafukufukuyu adapeza kuti zosungunulira zochepa kwambiri za organic sizingalepheretse kutulutsa, pomwe zosungunulira za organic zosungunulira zosungunulira zimatsogolera ku mawonekedwe achilendo pachimake chachikulu chifukwa cha zosungunulira.Only zolimbitsa organic zosungunulira akhoza kuwonjezeredwa kuti bwino kuteteza succinic asidi Solifenacin ndi adsorbed pa galasi, kuwonjezera 50% methanol kapena Mowa kapena 30% ~ 50% acetonitrile akhoza kugonjetsa ofooka mogwirizana pakati pa mankhwala ndi padziko vial.
PP Mbale Zagalasi Mbale Zagalasi Zagalasi Mbale Zagalasi Mbale Zagalasi
Nthawi yosungira 0h 0h 9.5h 17h 48h
30% acetonitrile 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% methanol 835.8 825 825.6 825.8 823.1
Table 4 Zotsatira za zosungunulira zosiyanasiyana za organic pa ma adsorption a mabotolo agalasi
kuti solifenacin succinate imasungidwa mu njira yothetsera.Table 4 manambala
Zasonyezedwa kuti pamene solifenacin succinate amasungidwa mu galasi Mbale, ntchito
Pambuyo organic zosungunulira njira ya chitsanzo pamwamba kuchepetsedwa, ndi succinate mu galasi Mbale.Malo apamwamba a linacin mkati mwa 48h ndi ofanana ndi malo apamwamba a PP vial pa 0h.Pakati pa 0.98 ndi 1.02, deta ndi yokhazikika.
3.0 pomaliza:
Mitundu yosiyanasiyana ya Mbale zamagalasi zofooka zofooka za succinic acid Solifenacin zidzatulutsa madigiri osiyanasiyana a adsorption, kutsatsa kumayamba chifukwa cha kuyanjana kwa magulu a protonated amine okhala ndi magulu aulere a silanol.Chifukwa chake, nkhaniyi imakumbutsa makampani oyesa mankhwala kuti pakusungirako kapena kusanthula kwamadzimadzi, onetsetsani kuti mwayang'ana kutayika kwa mankhwala, pH yoyenera yothira kapena pH yoyenera kufufuzidwa pasadakhale.Chitsanzo kotero kuti zosungunulira oganic kupewa kugwirizana pakati pa mankhwala zofunika ndi galasi, kuti achepetse kukondera deta pa kusanthula mankhwala ndi kukondera chifukwa pa kafukufuku.
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[4] El-Shamy TM.Gawo lodziwikiratu pakuchitapo kanthu kwa magalasi a silicate.
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[6] Bacon FR, Raggon FC.Kukwezeleza kwa Attack on Glass ndi Silika ndi Citrateand
Ma Anions Ena mu Neutral Solution.J AM
Chithunzi 4. Kuyanjana pakati pa gulu la protonated amino la solifenacin ndi magulu olekanitsidwa a silanol pagalasi.
Nthawi yotumiza: May-26-2022