Nhanganyaya

Muchigadzirwa chekugadzira mishonga, zvinonyungudutsa zvinoshandiswa zvakanyanya muzvikamu zvakawanda zveAPI synthesis, kubvisa, kucheneswa uye maitiro ekugadzirisa. Zvisinei, kana izvi zvinonyungudutsa zvisikwa zvisina kubviswa zvachose kubva pachigadzirwa chekupedzisira, "zvinosara zvinonyungudutsa" zvichaumbwa. Zvimwe zvinonyungudutsa zvine chepfu, carcinogenicity kana zvimwe zvingangove nengozi dzehutano, saka, kudzora kwakasimba kwezviri mukati mezvakasara zvinonyungudutsa mumishonga haisi chinhu chakakosha chinongedzo chekuchengetedza kuchengetedzwa kwemishonga yevarwere, asiwo chikamu chakakosha chehutano hwekutonga kwemishonga.

Mukuongorora kwepamusoro, sampu yakavharwa mune chaiyo mudziyo wekudziya, kuitira kuti zvikamu zvinoputika zvibudiswe munzvimbo yegesi pamusoro pechigadziko, uye ipapo gasi iri rinopinzwa mugasi chromatograph kuti riongororwe. Kuvimbika uye kurongeka kweichi nhanho inoita seiri nyore kunoenderana zvakanyanya pane kiyi inobatika - headspace vials.

Mhedziso yeResidual Solvent Analysis Methods

Izvo zvakasiyana-siyana zvakasara zvinonyungudutsa zvinogona kunge zviripo mumishonga yemishonga, ine toxicological properties yakasiyana-siyana, inoda kuiswa mumapoka uye kutungamirirwa maererano nenjodzi dzayo kana ichiongororwa uye ichidzorwa. International peer-reviewed classification zviyeuchidzo zvinoisa zvakasara zvinonyungudutsa muzvikamu zvitatu zvinotevera:

1. Kirasi 1: Zvinorambidzwa zvinonyungudutsa

Kusanganisira benzene, methylene chloride, 1,2-dichloroethane, carbon tetrachloride, zvichingodaro, zvine carcinogenicity yakasimba uye njodzi dzezvakatipoteredza, zvinofanirwa kudzivirirwa pakugadzira. Miganhu inodzorwa zvakanyanya uye inowanzoverengerwa pamappm mazinga kana kunyange kuderera.

2. Kirasi 2: Zvinonyungudutsa zviri pasi pekutonga kushoma

Kusanganisira toluene, acetonitrile, DMF, isopropyl doro uye zvichingodaro. Zera rezvinonyungudutsa izvi rinogamuchirwa pasi pemiganho yakati, asi zvichine njodzi dzehuchetura. Miganhu inotarwa yakavakirwa paADI uye kazhinji inoda kunyatsotariswa.

3. Kirasi 3: Low toxicity solvents

Izvi zvinosanganisira ethanol, propanol, ethyl acetate, nezvimwewo, izvo zvine huturu hushoma kuvanhu uye zvinowanzoonekwa zvakachengeteka kumishonga kusvika ku50 mg yezuva nezuva.

Kuti unyatsoona mhando uye zviri mukati mezvisaririra izvi zvinonyungudutsa, gasi chromatography (GC) parizvino ndiyo inonyanya kufarirwa nzira yekuongorora, iyo ine zvakakosha zvakakosha zvekunzwa kwakanyanya, kugona kukuru kwekuparadzana, uye kushanda kune zvinosanganiswa zvinosanganiswa, izvo zvinogona kusangana nezvinodiwa zvekusarira kunyungudika kwekuongorora kutsvaga kutsvaga.

Pakati peakasiyana majekiseni modhi yemeteorological chromatography, headspace jekiseni tekinoroji inoshandiswa zvakanyanya mukuonekwa kwezvakasara zvinonyungudutsa mumishonga. Iyo tekinoroji kuburikidza nerudo rweiyo sampuli yakavharirwa mumusoro bhodhoro, inopisa kusvika kune yakakodzera tembiricha, ndiyo inonyungudutsa mune yemuenzaniso volatilization munzvimbo yebhodhoro gasi, uyezve kubva panzvimbo yekubvisa imwe vhoriyamu yegesi yakakweretwa muGC kuti iongororwe.

Zvakanakira zveheadspace feeding zvinosanganisira:

• Yakaderedzwa sampuli pre-kurapwa: hapana yakaoma solvent extraction kana dilution mashandiro anodiwa uye samples dzinogona kudziyisa zvakananga mukamuri yakavharwa;
• Kuvandudza kuberekana uye kugadzikana: nekunyatso kudzora tembiricha yekudziya uye nguva, iyo sampuli kusagadzikana inowirirana, inoderedza zvikanganiso zvekushanda;
• Kudzivirira kusvibiswa kana kukuvara kwekoramu: chikamu chegasi chete chinopinzwa muchromatography system, iyo inoderedza zvakanyanya kupindira kwezvikamu zvisingaite nekoramu uye detector.
• Inokodzera kuongororwa otomatiki: iyo headspace jekiseni system inogona kunge yakabatana zvisina mutsetse kune autosampler, yakakodzera kune yakakwira yekubuda yekuona zvinodiwa.

Nekudaro, yakagadzikana uye yakavimbika sampuli mudziyo, headpace vials, yakakosha pakuongorora uye kwakaringana headspace kuongororwa, iyo isingangotongi maitiro ekudzikisira uye kuisa chisimbiso chemuenzaniso, asi zvakare inobata zvakananga mhinduro yekupedzisira.

Tsanangudzo uye Mhedzisiro yeHeadspace Vials

Mune iyo headspace sampling nzira, kudziyisa uye kuvhuvhuta kwesample uye gasi nzvimbo yekutora maitiro zvese zvinoitika mumusoro mbichana senge midziyo isingavharwe nemhepo, kunyangwe ichiita senge yakapusa, asi magadzirirwo uye kuita kweiyo headspace vials zvine mhedzisiro yekuvimbika kwese kwekuongorora maitiro.
Headspace mabhodhoro ndiwo emuenzaniso mavhoriyamu akagadzirirwa headspace jekiseni mugasi chromatography. Kuvakwa kwayo kwakajairika kunosanganisira zvikamu zvinotevera:

Bhodhoro: inowanzogadzirwa negirazi yepamusoro yeborosilicate, ine yakanaka yakakwirira tembiricha kuramba uye inertness kemikari, inowanzowanikwa mu10ml, 20ml, kana mavhoriyamu makuru;

Bhodhoro kuvhura/shinda: kazhinji yakajairwa 20mm kuvhura, yakakodzera aluminium caps uye autosampling masisitimu;

Cap: kazhinji yakatsikirirwa kubva kune inowirirana zvinhu kuti ive nechokwadi chekuomarara kwebhodhoro;

Gasket: kune PTFE uye silicone composite zvinhu kuumbwa, ine yakanaka yakakwira tembiricha kuramba uye makemikari inertness, inogona kumira akawanda puncture sampling pasina kuvuza.

Basa guru rebhodhoro remusoro nderekupa nzvimbo yakavharwa, inert uye inodzorwa, ndiyo inonyungudutsa inonyungudutsa mumuenzaniso pasi pemamiriro ekupisa ndiyo nzira oh bhodhoro pamusoro penzvimbo yegesi, kuumbwa kwegasi kuenzana kwemumiriri weiyo solvent concentration mumuenzaniso wekutanga.

Kunyanya, basa rayo rinoratidzwa mune zvinotevera zvinhu:

Chisimbiso garandi: chisimbiso chakanaka kuti uve nechokwadi chekuti sampuli mukudziya kana kuzorora nguva dzose haizove nekuda kwekudonha uye kurasikirwa kwekunyungudika;

Inert zvinhu kudzivirira: girazi remhando yepamusoro uye gasket zvinhu zvinodzivirira kuita nemuenzaniso kana solvent, kudzivisa kuiswa kwezvinyorwa zvenhema kana kupindira kwechiratidzo;

Constant volume conditions: mabhodhoro akamisikidzwa anobatsira pakugadzikana kwemusoro uye kuberekana, kufambisa huwandu uye kuenzanisa kwemhedzisiro yekuongorora.

Headspace vials pessimistic antipathy inoshandiswa kune otomatiki headspace sampler. Kufambiswa kwebasa kunowanzoita sezvizvi:

1. Mhinduro yemuenzaniso inowedzerwa kune headspace vial uye yakavharwa;
2. Iyo autosampler inodyisa vial mu thermostatic heat module;
3. Sample inodziyirwa mubhodhoro kusvika kune tembiricha yakatarwa uye iyo inoputika zvikamu zvinotamira mumusoro;
4. Tsono yejekiseni inobaya gasket uye inokwevera huwandu hwegasi kubva kumusoro;
5. Iyo gasi inopinzwa mugasi chromatograph yekuparadzanisa alarm uye kuona.

Mukuita uku, kugadzikana kwechimiro, gasket puncture performance, uye kuiswa chisimbiso kweiyo headspace vials zvine hukama zvakananga nekuenderana kwesampling uye nekururama kwemuenzaniso. Kunyanya, kushandiswa kweakamisikidzwa, akavimbika headpace mabhodhoro mumabasa otomatiki kwakakosha pakuona kuti maitiro ekuongorora anofamba zvakanaka uye kuderedza mitengo yekukundikana.

Nei Headspace Vials ichikosha?

Kunyangwe iyo gasi chromatograph uye detector iri iyo yakakosha midziyo mukusarira solvent kuongorora, basa reiyo headspace vial rakakosha zvakaenzana. Semutakuri wevanoongorora kubva kumuenzaniso pretreatment kune jekiseni, kuita kwayo kwakanangana nekugadzikana kweiyo yese analytical system uye kuvimbika kweiyo data.

1. Sample kutendeseka uye volatility kudzora

Zvisaririra zvinonyungudutsa zvinonyanya kufashaira, organic volatile compounds izvo zvinonyanya kurasika panguva yekuratidzwa, kupisa kana kuchengetedza. Kana iyo headpace vials isina kuchengetwa muchisimbiso chakasimba mukati mekutenderera kwekuongorora, iyo solvent yemukati inogona kuchinja, zvichikonzera mhedzisiro.

High-quality headpace vials inogona kupisa kusvika kune 100-150 ° C munzvimbo yakavharwa, kuve nechokwadi chokuti zvikamu zvinoputika zvinongobudiswa uye kuongororwa pasi pemamiriro ezvinhu akaiswa;

Kudzora kwakaringana kwesample kuti isvike gasi-liquid equilibrium pane inogara tembiricha uye vhoriyamu inowedzera kurongeka uye kuberekazve kwemhedzisiro.

2. Pesvedzero yekuisa chisimbiso kuita pane analytical results

Iyo yekuisa chisimbiso yeHeadspace vial inowanzo kuve nezvikamu zvitatu: cap, gasket uye muromo. Chisimbiso chisina kunaka pane imwe nguva chinogona kukonzera kuvhuvhuta kwemuenzaniso, ruzha rwekumashure, kana kunyange sampuli yekusvibiswa.

High-quality PTFE / silicone gaskets haisi kungopikisa kutonhora kwepamusoro uye makemikari, asi inogonawo kumira punctures yakawanda uye kuchengetedza chisimbiso chakanaka;

A low quality gasket kana loose gland inogona kukonzera solvent kutiza isati yaongororwa kana panguva yekupisa, inobata zvakananga nzvimbo yepamusoro uye kuderedza kuwanda kwehuwandu.

3. Kuenderana ne autosampling systems

Otomatiki headspace majekiseni anowanzo shandiswa mumarabhoritari emazuva ano kuvandudza kushanda nesimba uye kuenderana kwemhedzisiro, uye iyo Headspace vial's yakamisikidzwa dhizaini inobvumira kuti igadziriswe zvakananga kune makuru mhando dzejekiseni masisitimu.

Izvo zviyero zvakamisikidzwa zvinovimbisa kuti mabhodhoro anogona kungoonekwa otomatiki, akanyatso kumisikidzwa uye kubaiwa mune jekiseni;

Kuderedza zvikanganiso zvemanyorero kunonatsiridza kuenzanisa kugadzirisa uye kuenderana kwedhata, zvichiita kuti Headspace vial yakanakira yemhando yepamusoro-yekuyedza mamiriro.

4. Kemikari inertness yezvinhu

Iyo chemistry yemabhodhoro uye yekuisa chisimbiso zvinhu hazvifanirwe kufuratirwa kana uchiongorora trace solvents zvakare. Zvinhu zvisina kunaka zvemhando yepamusoro zvinogona kushambadza kana kuita nemamorekuru ekunyungudutsa, zvichitungamira kune zvakarerekera.

Borosilicate girazi ikemikari inert uye thermally stable, kudzivirira solvent adsorption kana kupisa kwekushisa;

Kune mamwe masisitimu akakosha ekunyungudutsa, gaskets akagadzirwa neakakosha zvinhu anodiwa kuti ave nechokwadi chekuona kunzwa uye kugadzikana kwemuenzaniso.

Iyo Headspace vial inopfuura kungori nyore sampuli mudziyo, chinhu chakakosha mukuona kuti mhedzisiro yekusarira yakanyungudika ongororo ndeyechokwadi, inowirirana uye inogoneka. Inotora mabasa akawanda anokosha mucheni yose yekuongorora, zvakadai sekuvhara chisimbiso, kudzora kwekugadzirisa, kuenzaniswa kwehurongwa, chibvumirano chemakemikari inertness, nezvimwewo. Icho chimwe chezvinhu zvisingagadziriswi zvekuona kuongororwa kwemishonga yepamusoro.

Zvinhu zvakakosha pakusarudza iyo Right Headspace Vial

Mukuongorora kwakasara kunyungudika, kusarudzwa kweakakodzera headspace vial chinhu chinodiwa kuti uve nechokwadi chechokwadi che data uye kuenderana kwemaitiro. Zvido zvekuyedza zvakasiyana, mhando dzemhando uye mapuratifomu ezviridzwa zvine zvakasiyana zvinodiwa zvemusoro wepamhepo vial zvinhu, chimiro uye kuita. Izvi zvinotevera zvakakosha zvinofanirwa kutariswa pakusarudza headspace vial:

1. Nyaya: girazi rudzi uye pachena

• Kirasi I borosilicate girazi: iyo yakasarudzika bhodhoro zvinhu zveyakasara solvent kuongororwa. Kupisa kwayo kwakanakisa uye kushomeka kwemakemikari uye kuderera kwakanyanya kweiyoni inonaya kunodzivirira kuita kwemakemikari pakati pezvinonyungudutsa nebhodhoro, kudzivirira manyepo enhema kana kupindira kwechiratidzo.
• Kujeka kwepamusoro kwebhodhoro: inobvumira kutarisa nekukurumidza kwechimiro chemuenzaniso panguva yekupuruzira, kuongorora kana kutarisa kwemhando, sekuvapo kwemvura, huwandu chaihwo hwemvura, nezvimwewo, pamwe nekuzivikanwa zviri nyore neatomatiki masisitimu.

2. Kusarudzwa kwevhoriyamu: zvinowanzoshandiswa zvinyorwa 10ml, 20ml

Kusarudzwa kweHeadspace vial simba kunofanirwa kuve kwakavakirwa pamusanganiswa wezvinotevera zvinhu:

• Sample volume: Kazhinji sampuli vhoriyamu inenge 50% yebhodhoro vhoriyamu kuti ive nechokwadi chakakwana headpace (gasi nzvimbo) yevolatilization equilibrium;
• Analytical Method Zvinodiwa: Semuenzaniso, iyo USP <467> yasara solvent nzira inokurudzira kushandiswa kwe20 ml headspace vial;
• Autosampler kuenderana: simbisa kuti bhodhoro rakasarudzwa rinotsigira chimbo chekushandisa chinoshandiswa, kunyanya bhodhoro riri pamusoro pekuvhura.

3. Chifukidzo chegasket rudzi: kuvhara uye kukodzera kwemakemikari

Gasket zvinhu: inonyanya kushandiswa ndeye PTFE composite gasket, iyo kaviri-layer structure inobatanidza kemikari inertia yePTFE ne elasticity yesilicone sealing, inogona kumira kupisa kwepamusoro-kupisa uye kuchengetedza chisimbiso chakanaka; kune yakasimba corrosive kana monstrous solvents, unogona kusarudza yakakwirira-kuchena PTFE layer yakasimbiswa gasket.

Mabhodhoro chivharo mhando: Aluminium caps akakodzera kune akawanda zviridzwa, ane tight gland uye yakanakisa chisimbiso; Magnetic caps akakodzera autosampling masisitimu ane magineti identification, ayo anobatsira kuvandudza kudyisa kunyatsoita uye kurongeka kwechokwadi; Treaded caps, nepo iri nyore kushandiswa kwemanyorero, inogona kusavharira pamwe chete nemhando dzegland uye inonyanya kuenderana nematanho ekusimudzira kana asiri epamusoro-kuburikidza mamiriro.

4. Reusability uye mutengo kufunga

Reusable glass vials (inoda kucheneswa kwepamusoro-tembiricha uye sterilization) inokodzera dzimwe nzira dzisiri dzepharmacopeial kana zvidzidzo zvekusimudzira uye dzinogona kuderedza mutengo wenguva refu;

Nekudaro, yekugadzira GMP kana yemhando yekudzora marabhoritari, mabhodhoro ekushandisa-kamwechete ari nani kuti ave nechokwadi chehutsanana uye kudzivirira kusvibiswa kwemuchinjiko;

Paunenge uchitenga mumabhechi, zvakakosha zvakare kuyera mhando yemhando, batch-to-batch kuenderana, uye mutengo wekusarudza mutengesi anopa chiyero chekuita uye mutengo.

Iyo inonzwisisika sarudzo yemusoro wepamhepo vial haingori basa rekutanga, asi zvakare chiratidzo chehunhu hwekudzora kuziva. Yese inoratidzika kunge diki parameter kusarudzwa inoita basa rakakosha mukurongeka kwemhedzisiro, kugadzikana kwehurongwa uye kushanda kwerabhoritari. Naizvozvo, kunzwisisa kwakadzama kwezvinhu izvi zvakakosha kugona kwehunyanzvi kune wese tekinoroji anoshanda mukuongororwa kwemishonga.

Mibvunzo Inowanzo bvunzwa uye Zvinyorwa

Kunyange zvazvo mabhodhoro emumusoro achishandiswa zvakanyanya mukusara kwekuongorora kunyungudika, nhevedzano yezvinetso inogona kuramba ichimuka mukuita nekuda kwekubata kusina kunaka kana kusarudzwa kwezvinhu zvinoshandiswa. Izvi zvinotevera matambudziko akajairika uye kurudziro yekudzivirira:

1. Nzira yekudzivirira sei sampuli yemuchinjikwa-kusvibiswa

Kusvibiswa kwepamuchinjikwa hakungogadziri kururamisa kwemigumisiro yekuongorora, asi kunogonawo kukonzera kupindira kwakavanzika kwenguva refu nehurongwa hwekutsvaga, kunyanya panjodzi yepamusoro paunenge uchiongorora mazinga akaderera. Matanho anotevera anogona kunzvenga dambudziko iri:

• Isa pamberi pekushandiswa kwemidziyo inoraswa uye cap pads: iyi ndiyo nzira yakananga uye inoshanda, kunyanya mukurapa kwemhando yemishonga uye yekudzora kuyedzwa;
• Tsiva kana kunyatsochenesa mabhodhoro akashandiswa zvakare: kana kushandiswazve kuchidiwa, iva nechokwadi chokuti yakanyatsocheneswa uchishandisa matanho akadai semvura yakasvibiswa, organic solvents, uye kupisa kwakanyanya kwekuomesa;
• Kugovera kwakasimba maitiro: shandisa maturusi epombi akasarudzika kudzivirira kudonhedza sampuli pamusoro kana kutenderedza bhodhoro;
• Chenesa bhenji rekushandisa kumusoro uye magurovhosi: pakubata zvinonyungudutsa zvinonyungudutsa, magirovhosi anofanira kuchinjwa nguva dzose kudzivirira kupararira kusvibiswa kuburikidza nekubata.

2. Kudonha kwecap panguva yekupisa

Mukuongorora nzvimbo yemusoro, sampuli inoda kudziyisa kusvika 80-120 ° C kana kutopfuura. Kana zvivharo kana gaskets zvisina kuvharwa zvakanaka, zvinonyungudutsa zvinogona kupukunyuka panguva yekudziya, zvichikonzera kuchinja-chinja kwedata kana mhedzisiro yakaderera.

• Sarudza emhando yepamusoro gaskets: ivo vanofanirwa kuve neakanaka kupisa kupisa uye puncture elasticity kuve nechokwadi kuti chisimbiso hachisununguke;
• Chakarurama capping simba: manual kana otomatiki capping inoda kuva pakati nepakati, yakasununguka inogona kudonha, yakanyanyisa inogona kuparadza gasket kana kukonzera bhodhoro kuputika;
• Kugara uchiongorora tsono yefeed system: tsono yakasakara kana yakaremara inogona kudzivirira gasket kubva pakuzvisunga, zvichikonzera kuvuza;
• Kugadziriswa kwekushisa kunonzwisisika: haifanirwe kudarika muganho wepamusoro wekupokana kwekushisa kwe gasket kana cap, kazhinji inodzorwa muhuwandu hwe110-130 ℃ yakachengeteka.

3. Vial yekuchenesa nekuchengetedza mazano

Nekushandisazve vial iyo inogona kuve nechekuita mukudzora mutengo kana chikamu chekuvandudza nzira, kutarisisa kwakanyanya kunoda kubhadharwa pakuchenesa nekuchengetedza maitiro kudzivirira kuunzwa kwetsvina kana zvakasara zvinonyungudutsa:

• Mazano ekuchenesa matanho: simbura kakawanda nemvura yakasvibiswa; sukurudza neakakodzera organic solvents; ultrasonic kuchenesa zvichienderana nehuwandu hwekusvibiswa; tembiricha yekuomesa pa105 ℃-120 ℃ kuve nechokwadi chekuti hapana chakasara mwando kana chinonyungudutsa.
• Kurudziro yekuchengeta: yakachena, yakaoma uye yakavharwa kuchengetedza, kudzivirira guruva, zvinhu zvinoputika zvakare kusvibiswa; usati washandiswa kana wakachengetwa kwenguva yakareba, zvinokurudzirwa kuongorora zvakare uye kuchenesa zvakare; kudzivirira kuratidzwa kwenguva refu kuchiedza chezuva kana kupisa kwakanyanya, kudzivirira kuparara kwegirazi kana kuchembera gasket.

Nekugona aya makiyi ekuita basa, haugone kungovandudza iko kurongeka uye kudzokorora kwebvunzo, asi zvakare zvinobudirira kuwedzera hupenyu hwesevhisi yemidziyo uye kuderedza chiyero chekutadza. Kune zvinhu zvekuongorora zvakadai sezvakasara zvinonyungudutsa, izvo zvinonyanya kunzwisiswa kutsvaga kusiyana-siyana, hutungamiri hwakadzama hwehumwe humwe hunoshandiswa hunofanira kuregeredzwa.

Mhedziso

Munzvimbo yakanyatsogadziriswa uye chaiyo yekuongororwa kwe solvent yezvisaririra zvemishonga, iyo headspace vial, kunyangwe idiki, inoita basa rinokosha uye rakakosha. Kubva pakuchengetedza, kuisa chisimbiso uye kupisa kwemuenzaniso, kune kuwirirana ne autosampling system, ndiyo yekutanga mutsara wekudzivirira muketani yose yekuongorora kuti ive nechokwadi chechokwadi che data.

Hunhu headpace mabhodhoro haango chengetedza kutendeseka kwesample, kudzivirira kurasika kurasikirwa, uye kunatsiridza kuenderana kwejekiseni, asi zvakare hwaro hunodiwa hwekunyatso kudhirowa uye kunzwisiswa kwekuona mukuongororwa otomatiki. Kunyanya kana uchibata netrace level quantitative analysis inodikanwa ne pharmacopoeia zviyero, diki chivharo chakakanganisika, zvisina kunaka zvinhu, kana kunyange isinga fungidzike sampuli yekuzadza oparesheni ichave isina-inoregeredza kukanganisa pamhedzisiro yekuongorora.

Sezvo kuvandudzwa kwezvinodhaka uye kutonga kwemhando kuri kuramba kuchiwedzera dhigirii reotomatiki uye yekuona kubuda, mazinga emhando yezvivharo zvemusoro ari kusimudzwa. Kubva pakuchena kwezvinhu, kuenderana kwezita kusvika pakuenderana kwehurongwa, remangwana headpace mabhodhoro haafanire kungogadzikana uye akavimbika, asi zvakare kutamba basa re "standardized interface" murabhoritari yekuronga, kubatsira data traceability, nzira yekubereka uye kuwedzera kukwidziridzwa kwekutonga kwemhando.