Mea kākau / 1,2 Hu Rong 1 Hol pahu Drum Song Xuezhi ma mua o ka huakaʻi 1 Jinsong 1 – ʻO ka 1, 2 hou
【Abstract】 ʻO ke aniani Borosilicate he mea hoʻohana nui ʻia a me ka pahu hoʻonā i ka ʻoihana lāʻau.ʻOiai loaʻa iā ia nā hiʻohiʻona o ke kūpaʻa kiʻekiʻe, e like me ka maʻalahi, ke kūpaʻa ʻana a me ke kūpaʻa ʻaʻahu, hiki i nā ion metala a me nā hui silanol i loko o ke aniani borosilicate ke launa pū me nā lāʻau lapaʻau.I ka nānā ʻana i nā lāʻau kemika e ka high performance liquid chromatography (HPLC), ʻo ke aniani borosilicate ka hue wai maʻamau.Ma ka noiʻi ʻana i ka hopena o nā hue aniani HPLC o ʻekolu mau lama i ke kūpaʻa ʻana o ka solifenacin succinate i kahi pūhui alkaline nāwaliwali, ua ʻike ʻia aia ka adsorption i nā lāʻau alkaline i loko o nā hue aniani i hana ʻia e nā mea hana like ʻole.ʻO ka adsorption ka mea nui ma muli o ka launa pū ʻana o ka amino protonated a me ka hui silanol dissociative, a ʻo ke kū ʻana o ka succinate i hāpai ʻia.Hiki i ka hoʻohui ʻana o ka waika hydrochloric ke hoʻopau i ka lāʻau lapaʻau a i ʻole ka hoʻohui ʻana i ka ʻāpana kūpono o nā mea hoʻoheheʻe kūlohelohe hiki ke pale i ka adsorption.ʻO ke kumu o kēia pepa e hoʻomanaʻo i nā ʻoihana hoʻāʻo lāʻau e hoʻolohe i ka launa ʻana ma waena o nā lāʻau alkaline a me ke aniani, a e hōʻemi i ka deviation data a me ka hana noiʻi o ka deviation i kumu ʻole ʻia e ka ʻike ʻole o nā ʻano adsorption o nā hue aniani i loko. ke kaʻina hana o ka nānā ʻana i ka lāʻau.
Hua'ōlelo nui: Solifenacin succinate, amino group, HPLC glass vials, adsorb
ʻO ke aniani e like me ka mea hoʻopili i nā mea maikaʻi o ka maʻalahi, ka hoʻopau maʻalahi a me ka pale ʻana i ka corrosion.Corrosion, wear resistance, volume stability a me nā pono ʻē aʻe, no laila ua hoʻohana nui ʻia i ka noi lāʻau.Hoʻokaʻawale ʻia ke aniani lāʻau i ke aniani sodium calcium a me ke aniani borosilicate, e like me nā ʻāpana like ʻole i loko.Iwaena o lakou, soda lime aniani i loko o 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;ʻO ke aniani borosilicate he 70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O a me K2O a me 2% ~ 4% Al2O3.Loaʻa i ke aniani borosilicate ke kūpaʻa kemika ma muli o ka hoʻohana ʻana o B2O3 ma kahi o ka hapa nui o Na2O a me CaO
Ma muli o kona ʻano ʻepekema, ua koho ʻia ʻo ia ka ipu nui no ka lāʻau wai.Eia naʻe, hiki i ke aniani boronSilicone, ʻoiai me kona kūpaʻa kiʻekiʻe, hiki ke launa pū me nā lāʻau lapaʻau.
1) Hoʻololi Ion: Na + , K + , Ba2 +, Ca2 + i loko o ke aniani e hoʻololi i ka ion me H3O + i loko o ka hopena, a aia ka hopena ma waena o nā ion i hoʻololi ʻia a me ka lāʻau lapaʻau;
2) ʻO ka hoʻoheheʻe ʻana o ke aniani: Phosphate, oxalate, Citrates a me nā tartrates e hoʻolalelale i ka hoʻoheheʻe ʻana o ke aniani a kumu i nā silicides.a ua hoʻokuʻu ʻia ʻo Al3+ i ka hopena;
3) Ka ʻino: EDTA i loko o ka lāʻau hoʻonā (EDTA) hiki ke paʻakikī me nā ion divalent a i ʻole nā iona trivalent i ke aniani.
4) Adsorption: Aia kahi paʻa Si-O haʻihaʻi ma ka ʻaoʻao aniani, hiki iā ia ke adsorb H +
Hiki i ka hoʻokumu ʻana o OH- ke hana i nā paʻa hydrogen me kekahi mau pūʻulu i loko o ka lāʻau lapaʻau, ka hopena o ka lāʻau i hoʻopili ʻia i ka ʻili aniani.
Loaʻa ka hapa nui o nā kinikini i nā pūʻulu amine nāwaliwali, I ka nānā ʻana i nā lāʻau kemika me ka hana kiʻekiʻe o ka wai chromatography (HPLC), ka pahu autosampler HPLC maʻamau i hana ʻia me ke aniani borosilicate, a ʻo ka hele ʻana o SiO- ma ka ʻili aniani e launa pū me ka pūʻulu amine protonated. , e 'ae ana i ka emi 'ana o ka lā'au lapa'au, 'a'ole pololei nā hualoa'a, a 'o OOS (Out of Specification).I loko o kēia hōʻike, ʻo ke kumu nāwaliwali (pKa ʻo 8.88 [2]) lāʻau solifenacin succinate (hōʻike ʻia ke ʻano hoʻohālikelike i ka Figure 1) i hoʻohana ʻia e like me ka mea noiʻi, a me ka mana o kekahi mau hue amber borosilicate glass injection ma ka mākeke ma ka loiloi lāʻau. ua hoʻokolokolo ʻia., a mai ka manao analytical e imi i ka hopena i ka adsorption o ia mau laau ma ke aniani.
1.Mahele ho'āʻo
1.1 Nā mea hana a me nā mea hana no nā hoʻokolohua
1.1.1 Mea Hana: Agilent High Efficiency me UV Detector
ʻO ka chromatography wai
1.1.2 Mea hoʻāʻo: Solifenacin succinate API i hana ʻia e Alembic
Pharmaceuticals Ltd. (India).Ua kūʻai ʻia ʻo Solifenacin standard (99.9% purity) mai USP.Ua kūʻai ʻia ʻo ARgrade potassium dihydrogen phosphate, triethylamine, a me phosphoric acid mai Kina Xilong Technology Co., Ltd. Ua kūʻai ʻia ka Methanol a me ka acetonitrile (ʻelua HPLC grade) mai Sibaiquan Chemical Co., Ltd. Ua kūʻai ʻia nā ʻōmole Polypropylene (PP) mai ThermoScientific (US) , a ua kūʻai ʻia nā ʻōmole aniani HPLC amber 2ml mai Agilent Technologies(China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., a me Zhejiang Hamag Technology Co., Ltd. (A, B, C i hoʻohana ʻia ma lalo nei. e hōʻike i nā kumu like ʻole o nā hue aniani, kēlā me kēia).
1.2HPLC kaʻina kālailai
1.2.1Solifenacin succinate a me solifenacin kumu manuahi: ke kolamu chromatographic isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3 µm.Me ka phosphate buffer (kaumaha 4.1 g o ka potassium dihydrogen phosphate, kaupaona 2 ml o ka triethylamine, e hoʻohui i ka 1 L o ka wai ultrapure, e hoʻoulu e hoʻoheheʻe, e hoʻohana i ka waikawa phosphoric (ua hoʻoponopono ʻia ka pH i 2.5) -acetonitrile-methanol (40:30:30) e like me ka pae kelepona,
Kiʻi 1 Ke kumu hoʻohālike o ka solifenacin succinate
Kiʻi 2 Ka hoʻohālikelike o nā wahi kiʻekiʻe o ka hopena like o ka solifenacin succinate i loko o nā hue PP a me nā hue aniani mai ʻekolu mau mea hana A, B, a me C.
ʻO ka mahana o ke kolamu he 30 ° C, he 1.0 mL / min ka kahe kahe, a ʻo ka nui o ka injection he 50 mL, ʻO 220 nm ka lōʻihi o ka hawewe.
1.2.2 Succinic acid sample: me ka hoʻohana ʻana i ka YMC-PACK ODS-A 4.6 mm × 150 mm, 3 µm kolamu, 0.03 mol/L phosphate buffer (hoʻololi ʻia i ka pH 3.2 me ka waikawa phosphoric)-methanol (92:8) e like me ka pae paʻa, kahe. ka helu 1.0 mL/min, ka mahana o ke kolamu 55 °C, a he 90 mL ka nui o ka injection.Loaʻa nā Chromatograms ma 204 nm.
1.3 ICP-MS kaʻina kālailai
Hoʻopili ʻia nā mea i loko o ka hoʻonā me ka hoʻohana ʻana i kahi ʻōnaehana Agilent 7800 ICP-MS, ʻo ke ʻano kānana he mode He (4.3mL/min), ʻo ka mana RF he 1550W, ʻo ka plasma gasflow rate he 15L/min, a me ke kahe o ke kinoea lawe. he 1.07mL/min.ʻO ka mahana wela o ka lumi noe he 2 ° C, ʻo ka piʻi peristaltic pump lifting / stabilizing speed he 0.3/0.1 rps, ka hāpana stabilizationtime he 35 s, ʻo ka manawa hāpai ʻana he 45 s, a ʻo ka hohonu o ka hōʻiliʻili ʻana he 8 mm.
Hoʻomākaukau laʻana
ʻO Solifenacin succinate solution: hoʻomākaukau ʻia me ka wai ultrapure, ʻo 0.011 mg/mL ka nui.
1.4.2 ʻO ka waiʻona Succinic: hoʻomākaukau ʻia me ka wai ultrapure, ʻo 1mg/mL ka ʻike.
1.4.3 Solifenacin solution: hoʻoheheʻe i ka solifenacin succinate i ka wai, hoʻohui ʻia ka sodium carbonate, a ma hope o ka hoʻololi ʻana o ka hopena mai ke keʻokeʻo tomilky kala ʻole, ua hoʻohui ʻia ka ethyl acetate.Hoʻokaʻawale ʻia ka papa ethyl acetate a hoʻoheheʻe ʻia ka solvent e hāʻawi i ka solifenacin.E hoʻoheheʻe i ka nui kūpono o ka solifenacin inethanol (ethanol no ka m 5% i ka hopena hope), a laila e hoʻoheheʻe me ka wai e hoʻomākaukau ai i ka hopena me kahi ʻano o 0.008 mg/mL solifenacin (me ka solifenacin succinate solution i loko o ka hopena e like me ka solifenacin. noonoo).
Nā hualoaʻa a me ke kūkākūkā
·········like kik. ··
2.1 Hiki i ka Adsorption o nā hue HPLC o nā hōʻailona like ʻole
E hoʻokaʻawale i ka wai wai like o ka solifenacin succinate i loko o nā hue PP a me 3 mau pahu autosampler vials i hoʻopaʻa ʻia i nā manawa i loko o ke kaiapuni like, a ua hoʻopaʻa ʻia ka wahi kiʻekiʻe o ka piko nui.Mai nā hualoaʻa ma ka Figure 2, hiki ke ʻike ʻia he kūpaʻa ka wahi kiʻekiʻe o nā hue PP, a ʻaneʻane ʻaʻohe loli ma hope o 44 h. ʻOiai ʻo nā wahi kiʻekiʻe o nā pahu aniani ʻekolu i ka 0 h ua liʻiliʻi ma mua o ka hue PP. , a ke emi nei ka piko i ka wā mālama.
Kiʻi 3 Nā hoʻololi i nā wahi kiʻekiʻe o ka solifenacin, succinic acid, a me ka solifenacin succinate wai hoʻonā i mālama ʻia i loko o nā hue aniani a me nā hue PP.
No ka noiʻi hou aku i kēia hanana, solifenacin, succinate acid, Aqueous solutions of solifenacin acid and succinate in glass vials of manufacturer Band PP bottles e noiʻi i ka hoʻololi ʻana o ka wahi kiʻekiʻe me ka manawa, a ma ka manawa like ke aniani.
ʻEkolu mau hopena i loko o nā hue i hui pū ʻia me ka hoʻohana ʻana i kahi Agilent 7800 ICP-MSPlasma mass spectrometer no ka nānā ʻana i ka elemental.Hōʻike ka ʻikepili ma ke Kiʻi 3 ʻaʻole i hoʻopili ʻia nā hue i loko o ke aniani i loko o ka wai wai, akā hoʻopili i ka solifenacinFree base a me ka solifenacin succinate.ʻO nā hue aniani adsorb succinate.ʻOi aku ka ikaika o ka linacin ma mua o ka solifenacin free base, i ka manawa mua ʻO Solifenacin succinate a me solifenacin free base i loko o nā hue aniani.ʻO nā lakio o nā wahi kiʻekiʻe o nā hoʻonā i loko o nā hue PP he 0.94 a me 0.98.
Ua manaʻoʻiʻo ʻia hiki i ka ʻili o ke aniani silicate ke komo i kekahi wai, kahi i hui pū ʻia e kekahi wai me Si4+ ma ke ʻano o nā pūʻulu OH e hoʻokumu i nā hui silanol Ma ke ʻano o ke aniani oxide, hiki ʻole ke neʻe nā ion polyvalent, akā metala alkali (e like me Hiki ke neʻe ka Na+ ) a me ka honua alkaline (e like me Ca2+) ke ʻae ʻia nā kūlana, ʻoi aku ka maʻalahi o ka kahe ʻana o nā metala alkali, hiki ke hoʻololi me ka H+ adsorbed ma ka ʻili aniani a hoʻololi i ka ʻili aniani e hana i nā hui silanol [3-4].No laila, hiki i ka hoʻonui H+ ke hoʻonui i ka hoʻololi ion e hoʻonui i nā hui silanol ma ka ʻili aniani.ma ka papa 1, ua like ole ka ma'i'o o B, Na, a me Ca i loko o ka ha'ina mai ke kiekie a i ka ha'aha'a.he waika succinic, solifenacin succinate a me solifenacin.
hāpana B (μg/L) Na(μg/L) Ca(μg/L) Al(μg/L) Si(μg/L) Fe(μg/L)
wai 2150 3260 20 ʻAʻohe ʻike 1280 4520
Hoʻonā waika Succinic 3380 5570 400 429 1450 139720
Solifenacin Succinate Solution 2656 5130 380 ʻAʻohe ʻike 2250 2010
solifenacin solution 1834 2860 200 ʻAʻohe ʻike 2460 ʻAʻohe ʻike
Papa 1 Nā mea nui o ka solifenacin succinate, solifenacin a me succinic acid wai hoʻonā i mālama ʻia i loko o nā hue aniani no 8 lā.
Eia kekahi, hiki ke ʻike ʻia mai ka ʻikepili ma ka Papa 2 ma hope o ka waiho ʻana i loko o nā hue aniani no 24 mau hola, ua piʻi ka pH o ka wai.Kokoke loa keia hanana i ka manao maluna
ʻO ka Vial No. Hoʻihoʻi hou ʻana ma hope o ka waiho ʻana i loko o ke aniani no 71 mau hola
(%) Laki hoʻihoʻi ma hope o ka hoʻoponopono ʻana o PH
Vial 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
Papa 3 Ke kūlana desorption o ka solifenacin succinate ma hope o ka hoʻohui ʻana i ka waika
No ka mea hiki ke hoʻokaʻawale ʻia ka Si-OH ma ka ʻili aniani i SiO-[5] ma waena o ka pH 2 ~ 12, aʻo ka solifenacin e loaʻa i ka N i loko o kahi ʻakika Protonation (ana ʻia ka pH o ka wai o ka solifenacin succinate he 5.34, ka pH waiwai o ka solifenacin. ʻO ka hopena he 5.80), a ʻo ka ʻokoʻa ma waena o nā pilina Hydrophilic ʻelua e alakaʻi i ka adsorption lāʻau ma ka ʻili aniani (Fig. 3), ua hoʻopili ʻia ka solifenacin a ʻoi aku ka nui o ka manawa.
Eia hou, ua ʻike pū ʻo Bacon lāua ʻo Raggon [6] i loko o ka solution neutral, hydroxy acids me kahi hui hydroxyl i ke kūlana e pili ana i ka hui carboxyl Hiki i nā solutions paʻakai ke unuhi i ka silicion oxidized.I loko o ka molecular structure o ka solifenacin succinate, aia kahi hui hydroxyl e pili ana i ke kūlana o ka carboxylate, e hoʻouka i ke aniani, lawe ʻia ʻo SiO2 a hoʻopau ʻia ke aniani.No laila, ma hope o ka hoʻokumu ʻana o ka paʻakai me ka waikawa succinic, ʻoi aku ka ʻike o ka adsorption o ka solifenacin i ka wai.
2.2 Nā ala e pale aku ai i ka adsorption
pH manawa mālama
0h 5.50
24h 6.29
48h 6.24
ʻO ka papa 2 ka hoʻololi ʻana o ka pH o nā wai wai o ka solifenacin succinate i loko o nā hue aniani
ʻOiai ʻaʻole e hoʻopili ʻia nā hue PP i ka solifenacin succinate, akā i ka wā o ka mālama ʻana i ka hopena i loko o ka hue PP, ua hana ʻia nā kiʻekiʻe haumia ʻē aʻe a ʻO ka hoʻolōʻihi ʻana o ka manawa mālama e hoʻonui mālie i ka wahi kiʻekiʻe o ka haumia, kahi i hoʻopilikia ai i ka ʻike ʻana o ka piko nui. .
No laila, pono e ʻimi i kahi ala e hiki ai ke pale i ka adsorption aniani.
E lawe i 1.5 mL o ka solifenacin succinate aqueous solution i loko o kahi hue aniani.Ma hope o ka waiho ʻia ʻana i loko o ka hoʻonā no 71 mau hola, ua haʻahaʻa nā helu hoʻihoʻi.E hoʻohui i ka 0.1M hydrochloric acid, e hoʻoponopono i ka pH ma kahi o 2.3, mai ka ʻikepili ma ka Papa 3. Hiki ke ʻike ʻia ua hoʻihoʻi ʻia nā helu hoʻihoʻi i nā pae maʻamau, e hōʻike ana e hiki ke hoʻopaʻa ʻia ka hopena adsorption storagetime ma ka pH haʻahaʻa.
ʻO kekahi ala e hōʻemi i ka adsorption ma o ka hoʻohui ʻana i nā solvents organik.Hana 10%, 20%, 30%, 50% methanol, ethanol, isopropanol, acetonitrile i hoʻomākaukau ʻia ma kahi ʻano o 0.01 mg/mL i ka wai Solifenacin succinate.Hoʻokomo ʻia nā ʻōhua i luna i loko o nā hue aniani a me nā hue PP.Ma ka lumi wela Ua aʻo ʻia kona kūpaʻa.Ua ʻike ʻia ka hoʻokolokolo ʻana ʻaʻole hiki i ka mea hoʻoheheʻe organik ke pale i ka adsorption, ʻoiai ʻo ka mea hoʻoheheʻe organik ʻoi aku ka nui o ka solvent e alakaʻi i ke ʻano kiʻekiʻe o ka piko nui ma muli o ka hopena solvent.Hiki ke hoʻohui ʻia nā mea hoʻoheheʻe kūlohelohe maʻalahi e pale pono i ka waikawa succinic Solifenacin i hoʻopili ʻia ma ke aniani, hoʻohui i ka 50% methanol a i ʻole ethanol a i ʻole 30% ~ 50% acetonitrile hiki ke lanakila i ka pilina nāwaliwali ma waena o ka lāʻau lapaʻau a me ka ʻili o ka hue.
ʻO nā hue PP nā hue aniani ʻo nā hue aniani
Ka manawa mālama 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
Papa 4 Nā hopena o nā mea hoʻoheheʻe organik like ʻole i ka hoʻopili ʻana o nā ʻōmole aniani
ʻOi aku ka maikaʻi o ka mālama ʻia ʻana o ka solifenacin succinate i ka hopena.Papa 4 helu
Ua hōʻike ʻia i ka wā e mālama ʻia ai ka solifenacin succinate i loko o nā hue aniani, e hoʻohana
Ma hope o ka hoʻoheheʻe ʻia ʻana o ka solvent organic solution o ka laʻana i luna, ka succinate i loko o nā hue aniani.ʻO ka wahi kiʻekiʻe o ka linacin i loko o 48h ua like ia me ka wahi kiʻekiʻe o ka vial PP ma 0h.Ma waena o 0.98 a me 1.02, paʻa ka ʻikepili.
3.0 hopena:
ʻO nā ʻano like ʻole o nā kīʻaha aniani no ka mea nāwaliwali kumu hoʻohui succinic acid Solifenacin e hana i nā degere like ʻole o ka adsorption, ʻo ka adsorption ka mea nui ma muli o ka launa pū ʻana o nā pūʻulu amine protonated me nā pūʻulu silanol manuahi.No laila, hoʻomanaʻo kēia ʻatikala i nā hui hoʻāʻo lāʻau i ka wā o ka mālama ʻana i ka wai a i ʻole ka nānā ʻana, e nānā pono i ka nalowale o ka lāʻau lapaʻau, hiki ke noiʻi mua ʻia ka pH diluent kūpono a i ʻole ka pH diluent kūpono.He laʻana no nā mea hoʻoheheʻe oganic e pale aku i ka pilina ma waena o nā lāʻau lapaʻau maʻamau a me ke aniani, i mea e hōʻemi ai i ka ʻikepili i ka wā o ka nānā ʻana i ka lāʻau a me ka hopena i ka hoʻokolokolo.
[1] Nema S, Ludwig JD.Nā ʻano hana lāʻau lapaʻau - nā lāʻau lapaʻau makua: volume 3: nā hoʻoponopono, hōʻoia a me ka wā e hiki mai ana.3rd ed.Crc Press;2011.
[2] https://go.drugbank.com/drugs/DB01591
[3] El-Shamy TM.ʻO ka lōʻihi kemika o nā aniani K2O-CaO-MgO-SiO2, Phys Chem Glass 1973;14:1-5.
[4] El-Shamy TM.ʻO ka pae hoʻoholo i ka hana ʻana o nā aniani silicate.
Keaniani Phys Chem 1973;14:18-19.
[5] Mathes J, Friess W. Ka hopena o ka pH a me ka ikaika ionic ma IgG adsorption tovials.
Eur J Pharm Biopharm 2011, 78(2):239-
[6] Bacon FR, Raggon FC.Hoʻolaha ʻia ka hoʻouka ʻana i ke aniani a me ka silica e Citrateand
ʻO nā Anion ʻē aʻe i loko o ka Neutral Solution.J AM
Kiʻi 4. Ka pilina ma waena o ka pūʻulu amino protonated o solifenacin a me nā hui silanol dissociated ma ka ʻili aniani
Ka manawa hoʻouna: Mei-26-2022