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【Abstract】 Borosilicate iko bụ a ọtụtụ-eji nkwakọ ihe na ngwọta akpa na-emepụta ọgwụ ụlọ ọrụ.Ọ bụ ezie na ọ nwere njirimara nke nguzogide dị elu, dị ka ire ụtọ, nguzogide corrosion na iyi nguzogide, ion metal na silanol dị na iko borosilicate nwere ike ka na-emekọrịta ihe na ọgwụ.N'ime nyocha nke ọgwụ kemịkal site na chromatography mmiri dị elu (HPLC), vial a na-ahụkarị bụ iko borosilicate.Site n'inyocha mmetụta nke HPLC iko vial nke atọ ụdị na nkwụsi ike nke solifenacin succinate nke bụ ihe na-adịghị ike alkaline compound, a chọpụtara na adsorption na alkaline ọgwụ dị na iko vials mepụtara dị iche iche na-emepụta.Ihe kpatara mgbasa ozi a bụ n'ihi mmekọrịta nke amino acid protonated na dissociative silanol, na ọnụnọ nke succinate kwalitere ya.Mgbakwunye nke hydrochloric acid nwere ike mebie ọgwụ ahụ ma ọ bụ ịgbakwụnye akụkụ kwesịrị ekwesị nke ihe mgbaze organic nwere ike igbochi mgbasa.Ebumnuche nke akwụkwọ a bụ ichetara ụlọ ọrụ nyocha ọgwụ ka ha ṅaa ntị na mmekọrịta dị n'etiti ọgwụ alkaline na iko, na iji belata ngbanwe data na ọrụ nyocha nke nhụsianya kpatara enweghị ihe ọmụma nke njirimara adsorption nke karama iko na. usoro nyocha ọgwụ.
Isi okwu: Solifenacin succinate, amino group, HPLC iko vials, adsorb
Iko dị ka ihe nkwakọba ihe nwere uru nke ire ụtọ, nkwụsị dị mfe na nkwụsị nke corrosion.A na-ekewa iko ọgwụ na sodium calcium glass na iko borosilicate, dịka akụkụ dị iche iche dị na ya.N'ime ha, soda lime iko nwere 71% ~ 75% SiO2, 12% ~ 15% Na2O, 10% ~ 15% CaO;iko borosilicate nwere 70% ~ 80% SiO2, 7% ~ 13% B2O3, 4% ~ 6% Na2O na K2O na 2% ~ 4% Al2O3.Iko Borosilicate nwere ezigbo nguzogide kemịkalụ n'ihi iji B2O3 kama ọtụtụ Na2O na CaO.
N'ihi ọdịdị sayensị ya, a họọrọ ya dị ka ihe bụ isi maka ọgwụ mmiri mmiri.Agbanyeghị, iko boronSilicone, ọbụlagodi na nguzogide ya dị elu, nwere ike iji ọgwụ emekọrịta ihe, enwere usoro mmeghachi omume anọ dị ka ndị a [1]:
1) Ion mgbanwe: Na + , K+ , Ba2 +, Ca2 + na iko ime mgbanwe ion na H3O + na ngwọta, na e nwere mmeghachi omume n'etiti gbanwere ion na ọgwụ;
2) Mgbasa iko: Phosphate, oxalate, Citrates na tartrates ga-eme ka mgbasa nke iko mee ngwangwa na-akpata silicides.na Al3+ ka ewepụtara na ngwọta;
3) Corrosion: EDTA dị na ngwọta ọgwụ (EDTA) nwere ike gbagwojuru anya na ion divalent ma ọ bụ ion trivalent na iko.
4) Adsorption: Enwere njikọ Si-O gbajiri agbaji n'elu iko, nke nwere ike ịgbasa H +
Nhazi nke OH- nwere ike ịmepụta njikọ hydrogen na ụfọdụ otu dị na ọgwụ ahụ, na-eme ka a na-etinye ọgwụ ahụ n'elu iko.
Ọtụtụ kemịkalụ nwere otu amine ndị na-adịghị ike, mgbe ị na-enyocha ọgwụ kemịkalụ nwere chromatography mmiri dị elu (HPLC), vial HPLC autosampler a na-ejikarị eme ihe nke a na-eji iko borosilicate, yana ọnụnọ SiO- n'elu iko ga-eso ndị amine protonated emekọrịta ihe. , ikwe ka njupụta ọgwụ na-ebelata, nsonaazụ nyocha ga-abụ nke na-ezighi ezi, na ụlọ nyocha OOS (Ọpụghị nkọwapụta).N'ime akụkọ a, a na-eji isi ihe na-adịghị ike (pKa bụ 8.88 [2]) ọgwụ solifenacin succinate (usoro nhazi egosipụtara na Figure 1) dị ka ihe nyocha, na mmetụta nke ọtụtụ amber borosilicate iko injection vial na ahịa na nyocha ọgwụ. a na-enyocha ya., na site na nyocha echiche ịchọta ngwọta maka mgbasa ozi ọgwụ ndị dị otú ahụ na iko.
1.Nnwale akụkụ
1.1 Akụrụngwa na akụrụngwa maka nnwale
1.1.1 Akụrụngwa: Agilent High arụmọrụ na UV Detector
chromatography nke mmiri mmiri
1.1.2 Ngwa nnwale: Solifenacin succinate API bụ nke Alembic mepụtara
Pharmaceuticals Ltd. (India).Azụtara ọkọlọtọ Solifenacin (99.9% ịdị ọcha) n'aka USP.A zụtara ARgrade potassium dihydrogen phosphate, triethylamine, na phosphoric acid site na China Xilong Technology Co., Ltd. Methanol na acetonitrile (ma ọkwa HPLC) na Sibaiquan Chemical Co., Ltd. A zụtara karama Polypropylene (PP) na ThermoScientific (US) , na 2ml amber HPLC karama iko a zụtara site na Agilent Teknụzụ (China) Co., Ltd., Dongguan Pubiao Laboratory Equipment Technology Co., Ltd., na Zhejiang Hamag Technology Co., Ltd. (A, B, C na-eji n'okpuru ebe a). iji nọchite anya isi mmalite dị iche iche nke vials iko, n'otu n'otu).
1.2HPLC usoro nyocha
1.2.1Solifenacin succinate na solifenacin free base: kọlụm chromatographic isphenomenex luna®C18 (2), 4.6 mm × 100 mm, 3µm.Na phosphate buffer (atụ 4.1 g nke potassium dihydrogen phosphate, tụọ 2 ml nke triethylamine, tinye ya na 1 L nke ultrapure mmiri, bilie igbari, usephosphoric acid (pH na-agbanwe na 2.5) -acetonitrile-methanol (40:30:30). dị ka usoro mobile,
Ọgụgụ 1 Usoro nhazi nke solifenacin succinate
Ọnụọgụ 2 Ntụle mpaghara kachasị elu nke otu ngwọta nke solifenacin succinate na PP vial na iko iko sitere n'aka ndị nrụpụta atọ A, B na C.
Okpomọkụ kọlụm bụ 30 ° C, ọnụego eruba bụ 1.0 mL / min, na olu injection bụ 50 ml, ogologo ogologo oge nchọpụta bụ 220 nm.
1.2.2 Succinic acid sample: iji YMC-PACK ODS-A 4.6 mm × 150 mm, 3 µm kọlụm, 0.03 mol / L phosphate buffer (doziri na pH 3.2 withphosphoric acid) -methanol (92: 8) dị ka mobile usoro, na-asọpụta. ọnụego 1.0 ml/min, kọlụm okpomọkụ 55 Celsius C, na olu injection bụ 90 ml.E nwetara Chromatogram na 204 nm.
1.3 ICP-MS usoro nyocha
A na-enyocha ihe ndị dị na ngwọta ahụ site na iji usoro Agilent 7800 ICP-MS, ọnọdụ nyocha bụ ọnọdụ ya (4.3mL / min), ike RF bụ 1550W, ọnụego gasflow plasma bụ 15L / min, na ọnụ ọgụgụ na-ebu gas. bụ 1.07 ml / min.Igwe ikuku dị n'ime ụlọ ahụ dị 2 Celsius C, ịgbatị mgbapụta peristaltic na-ebuli / nkwụsi ike bụ 0.3 / 0.1 rps, oge nkwụsi ike bụ 35 s, oge ebuli ihe nlele bụ 45 s, omimi mkpokọta bụ 8 mm.
Nkwadebe ihe atụ
Solifenacin succinate ngwọta: nke a kwadebere na mmiri ultrapure, ntinye uche bụ 0.011 mg / ml.
1.4.2 Succinic acid ngwọta: kwadebere na ultrapure mmiri, ịta bụ 1mg/mL.
1.4.3 Solifenacin ngwọta: igbari solifenacin succinate na mmiri, agbakwunyere sodium carbonate, na mgbe ngwọta gbanwere site na-acha ọcha tomilky na-enweghị color, ethyl acetate.E kewapụrụ oyi akwa ethyl acetate ma wepụ ihe mgbaze iji nye solifenacin.Igbari solifenacin inethanol kwesịrị ekwesị (ethanol na-akpata m 5% na ngwọta ikpeazụ), wee jiri mmiri dozie ngwọta ya na ntinye nke 0.008 mg / ml solifenacin (ya na solifenacin succinate ngwọta dị na ngwọta dị ka solifenacin). itinye uche).
Nsonazụ na mkparịta ụka
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2.1 ike adsorption nke HPLC vials nke ụdị dị iche iche
Wepụ otu ngwọta mmiri nke solifenacin succinate n'ime vial PP na ụdị 3 nke autosampler vial ka a na-agbanye n'otu oge n'otu gburugburu ebe obibi, na-edekọ ọnụ ọgụgụ kasị elu nke isi.Site na nsonaazụ dị na eserese 2, enwere ike ịhụ na ọnụ ọgụgụ kachasị elu nke vials PP kwụsiri ike, ọ fọrọ nke nta ka ọ bụrụ mgbanwe ọ bụla mgbe awa 44 gasịrị. , na ebe kachasị elu na-aga n'ihu na-ebelata n'oge nchekwa.
Ọnụọgụ 3 Mgbanwe n'ebe kachasị elu nke solifenacin, succinic acid, na solifenacin succinate ngwọta nke a na-echekwa na vial ugegbe na PP vials.
Iji mụtakwuo ihe a, solifenacin, succinate acid, ngwọta mmiri nke solifenacin acid na succinate na iko iko nke emepụtara Band PP karama iji nyochaa mgbanwe nke elu mpaghara na oge, na n'otu oge ahụ iko.
A na-ejikọta ngwọta atọ dị na vials site na iji Agilent 7800 ICP-MSPlasma mass spectrometer maka nyocha elementrị.Ihe omuma a di na eserese 3 gosiputara na inglass vials nke di na mmiri mmiri anabataghi succinic acid, kama obu solifenacinFree base na solifenacin succinate.Glass vial na-anabata succinate.Ogo linacin siri ike karịa nke solifenacin free base, n'oge mbụ Solifenacin succinate na solifenacin free base na iko iko.Ọnụ ọgụgụ nke ebe kachasị elu nke ngwọta dị na karama PP bụ 0.94 na 0.98, n'otu n'otu.
A na-ekwenyekarị na elu nke iko silicate nwere ike ịmịnye mmiri ụfọdụ, nke ụfọdụ mmiri na-ejikọta ya na Si4 + n'ụdị OH dị iche iche na-emepụta ìgwè silanol N'ime ihe mejupụtara iko oxide, ion polyvalent enweghị ike ịkwaga, mana alkali metal (dịka ọmụmaatụ. Na + ) na alkaline earth metal ion (dị ka Ca2+) nwere ike ịkwaga mgbe ọnọdụ na-ekwe, karịsịa alkali metal ion dị mfe na-asọba, nwere ike ịgbanwe na H + adsorbed na iko elu na Nyefee na iko elu na-etolite silanol otu [3-4].Ya mere, ntinye H + nke mmụba nwere ike ịkwalite mgbanwe ion iji mee ka ìgwè silanol dị n'elu iko.site na table1 na-egosi na ọdịnaya nke B, Na, na Ca na ngwọta dịgasị iche site na elu ruo ala.bụ succinic acid, solifenacin succinate na solifenacin.
sample B (μg/L) Na (μg/L) Ca (μg/L) Al (μg/L) Si (μg/L) Fe (μg/L)
mmiri 2150 3260 20 Enweghị nchọpụta 1280 4520
Succinic acid ngwọta 3380 5570 400 429 1450 139720
Solifenacin Succinate Solution 2656 5130 380 Enweghị nchọpụta 2250 2010
Solifenacin ngwọta 1834 2860 200 Enweghị nchọpụta 2460 Enweghị nchọpụta
Tebụl 1 Nchịkọta ihe mejupụtara nke solifenacin succinate, solifenacin na ngwọta mmiri succinic acid echekwara na vial iko maka ụbọchị 8.
Na mgbakwunye, enwere ike ịhụ ya site na data dị na tebụl 2 na mgbe nchekwa na karama iko maka awa 24, agbazekwa pH nke mmiri mmiri bilitere.Ihe omume a dị nso na tiori dị n'elu
Vial Mba. Iweghachite ọnụego mgbe nchekwa na iko maka 71 h
(%) Ọnụego mgbake ka emezigharịrị 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
Tebụl 3 Ọnọdụ mbibi nke solifenacin succinate mgbe mgbakwunye acid gasịrị
Ebe ọ bụ na Si-OH dị n'elu iko nwere ike kewaa n'ime SiO-[5] n'etiti pH 2 ~ 12, ebe solifenacin na-eme N na gburugburu acidic Protonation (pH nke ngwọta mmiri nke solifenacin succinate bụ 5.34, pH uru nke solifenacin). ngwọta bụ 5.80), na ọdịiche dị n'etiti abụọ Hydrophilic mmekọrịta na-eduga na ọgwụ adsorption n'elu iko (Fig 3), solifenacin na-adsorbed ọzọ na oge.
Na mgbakwunye, Bacon na Raggon [6] chọpụtakwara na na ngwọta na-anọpụ iche, hydroxy acids nwere otu hydroxyl nọ n'ọnọdụ metụtara otu carboxyl Ngwọta Nnu nwere ike wepụ silicion oxidized.N'ime usoro ihe omimi nke solifenacin succinate, enwere otu hydroxyl n'ọnọdụ nke carboxylate, nke ga-awakpo iko ahụ, a na-ewepụta SiO2 wee mebie iko ahụ.Ya mere, mgbe emechara nnu na succinic acid, mgbasa ozi nke solifenacin na mmiri na-apụta ìhè karịa.
2.2 Ụzọ iji zere mgbasa ozi
Oge nchekwa pH
0h 5.50
24h 6.29
48h 6.24
Tebụl 2 pH mgbanwe nke ngwọta mmiri nke solifenacin succinate na karama iko
Ọ bụ ezie na PP vials adịghị adsorb solifenacin succinate, Ma n'oge nchekwa nke ihe ngwọta na PP vial, ndị ọzọ adịghị ọcha ọnụ ọnụ na-emepụta na ogologo oge nke nchekwa na-eji nwayọọ nwayọọ na-abawanye elu ebe adịghị ọcha, nke mere ka nnyonye anya na nchọpụta nke isi elu. .
Ya mere, ọ dị mkpa iji nyochaa usoro nke nwere ike igbochi mgbasa ozi iko.
Were 1.5 ml nke solifenacin succinate mmiri mmiri n'ime vial iko.Mgbe etinyechara ya na ngwọta maka awa 71, ọnụego mgbake niile dị ala.Tinye 0.1M hydrochloric acid, gbanwee pH na ihe dịka 2.3, site na data dị na Tebụl 3. Enwere ike ịhụ na ọnụego mgbake niile laghachiri na ọkwa nkịtị, na-egosi na mmeghachi omume adsorption oge nchekwa nwere ike igbochi na pH ala.
Ụzọ ọzọ bụ ibelata adsorption site n'ịgbakwunye ihe mgbaze organic.Mee 10%, 20%, 30%, 50% methanol, ethanol, isopropanol, acetonitrile kwadebere na ntinye nke 0.01 mg / ml na mmiri mmiri Solifenacin succinate.A na-etinye ihe ngwọta ndị a dị n'elu n'ime iko iko na PP vial, n'otu n'otu.N'ime ụlọ okpomọkụ, a mụrụ nkwụsi ike ya na-egosi.Nnyocha ahụ chọpụtara na ntakịrị ihe mgbaze organic enweghị ike igbochi mgbasa ozi, ebe ihe mgbaze organic nke ukwuu ga-eduga n'ụdị kachasị elu nke isi n'ihi mmetụta mgbaze.Naanị ihe mgbaze organic na-agafeghị oke nwere ike ịgbakwunye iji gbochie succinic acid nke ọma, a na-etinye Solifenacin na iko, tinye 50% methanol ma ọ bụ ethanol ma ọ bụ 30% ~ 50% acetonitrile nwere ike imeri mmekọrịta adịghị ike n'etiti ọgwụ na elu nke vial.
Mpempe akwụkwọ PP Glass Vials Glass Vials Glass Vials Glass Vials
Oge nchekwa 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
Isiokwu 4 Mmetụta dị iche iche organic solvents na adsorption nke iko iko
na solifenacin succinate ka edobere ya na ngwọta.Tebụl 4 nọmba
E gosiputara na mgbe a na-echekwa solifenacin succinate na vial iko, jiri ya
Mgbe organic ihe mgbaze ihe atụ n'elu na-diluted, na succinate ke iko vials.Ebe kachasị elu nke linacin n'ime awa 48 bụ otu ihe ahụ na mpaghara elu nke PP vial na 0h.N'etiti 0.98 na 1.02, data kwụsiri ike.
3.0 nkwubi okwu:
Ụdị enyo dị iche iche maka ihe na-adịghị ike succinic acid Solifenacin ga-emepụta ogo mgbasa ozi dị iche iche, mgbasa ozi na-abụkarị site na mmekọrịta nke otu amine protonated na otu silanol na-akwụghị ụgwọ.Ya mere, isiokwu a na-echetara ụlọ ọrụ nyocha ọgwụ na n'oge nchekwa mmiri ma ọ bụ nyocha, jide n'aka na ị ga-aṅa ntị na nkwụsị nke ọgwụ, pH kwesịrị ekwesị ma ọ bụ pH diluent kwesịrị ekwesị nwere ike nyochaa tupu oge eruo.Ọmụmaatụ maka ihe mgbaze oganic iji zere mmekọrịta dị n'etiti ọgwụ ndị bụ isi na iko, ka o wee belata nhụsianya data n'oge nyocha ọgwụ na nhụsianya na-akpata na nyocha.
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[2] https://go.drugbank.com/drugs/DB01591
[3] El-Shamy TM.Ogologo kemịkalụ nke iko K2O-CaO-MgO-SiO2, Phys Chem Glass 1973;14:1-5 .
[4] El-Shamy TM.Nzọụkwụ na-ekpebi ọnụego na dealkalisation nke silicateglasses.
Phys Chem Glass 1973;14:18-19 .
[5] Mathes J, Friess W. Mmetụta pH na ike ionic na tovials adsorption IgG.
Eur J Pharm Biopharm 2011, 78 (2): 239-
[6] Bacon FR, Raggon FC.Nkwalite mwakpo na Glass na Silica site na Citrateand
Ndị ọzọ Anions na Ngwọta Na-anọpụ iche.J AM
Ọgụgụ 4. Mmekọrịta dị n'etiti protonated amino group nke solifenacin na silanol iche iche nke kewara ekewa n'elu iko.
Oge nzipu: Mee-26-2022