ANALYTICK\u00dd V\u00ddZKUM A V\u00ddVOJ<\/h3><\/span><\/div><\/div><\/div>V\u00fdvoj analytick\u00fdch metod, analytika ne\u010distot, studie degradace, stopov\u00e9 anal\u00fdzy a dal\u0161\u00ed.
\nPomoc\u00ed na\u0161ich analytick\u00fdch znalost\u00ed a nejmodern\u011bj\u0161\u00edho vybaven\u00ed podporujeme klienty b\u011bhem v\u00fdvoje a registrace jejich l\u00e9k\u016f podle nejnov\u011bj\u0161\u00edch trend\u016f v analytick\u00e9 chemii.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
- V\u00fdvoj analytick\u00fdch metod<\/div><\/a><\/li>
- Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/div><\/a><\/li>
- Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/div><\/a><\/li>
- Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/div><\/a><\/li>
- Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/div><\/a><\/li><\/ul><\/div>
- V\u00fdvoj analytick\u00fdch metod<\/div><\/a><\/li><\/ul><\/div>\n
V\u00fdvoj analytick\u00fdch metod<\/h2>\n
Jako ka\u017ed\u00e1 \u00fasp\u011b\u0161n\u00e1 spole\u010dnost mus\u00edme b\u00fdt efektivn\u00ed, flexibiln\u00ed a modern\u00ed. P\u0159esn\u011b v tomto duchu pracuje i na\u0161e odd\u011blen\u00ed v\u00fdvoje a v\u00fdzkumu. Jsme kompaktn\u00ed a inovativn\u00ed t\u00fdm expert\u016f. P\u0159i sv\u00e9 pr\u00e1ci pou\u017e\u00edv\u00e1me modern\u00ed p\u0159\u00edstrojovou techniku a sledujeme nejnov\u011bj\u0161\u00ed trendy v oblasti analytick\u00e9 chemie, ale nezapom\u00edn\u00e1me ani na star\u00e9 dobr\u00e9 chemick\u00e9 postupy.<\/p>\n
V\u00fdvoj analytick\u00fdch metod
\n<\/strong>V\u00fdvoje a testov\u00e1n\u00ed nov\u00fdch analytick\u00fdch metod p\u0159edstavuje t\u011b\u017ei\u0161t\u011b na\u0161\u00ed \u010dinnosti. Nej\u010dast\u011bj\u0161\u00ed d\u016fvody pro v\u00fdvoj analytick\u00e9 metody, se kter\u00fdmi se v praxi setk\u00e1v\u00e1me, jsou n\u00e1sleduj\u00edc\u00ed:<\/p>\n\n- P\u0159i v\u00fdvoji nov\u00e9 (patentov\u011b nechr\u00e1n\u011bn\u00e9) syntetick\u00e9 cesty k \u00fa\u010dinn\u00e9 l\u00e1tce je pot\u0159eba sledovat reak\u010dn\u00ed konverze a profily ne\u010distot u meziprodukt\u016f i fin\u00e1ln\u00edho produktu.<\/li>\n
- Analytick\u00e1 metoda pro stanoven\u00ed \u010distoty nebo obsahu fin\u00e1ln\u00ed \u00fa\u010dinn\u00e9 l\u00e1tky popsan\u00e1 v p\u0159\u00edslu\u0161n\u00e9m l\u00e9kopise je zastaral\u00e1 nebo nespl\u0148uje po\u017eadavky z\u00e1kazn\u00edka.<\/li>\n
- Nen\u00ed k dispozici vhodn\u00e1 metoda na stanoven\u00ed \u010distoty nebo obsahu \u00fa\u010dinn\u00e9 l\u00e1tky v nov\u00e9m l\u00e9\u010div\u00e9m p\u0159\u00edpravku.<\/li>\n
- Fin\u00e1ln\u00ed l\u00e9\u010divo je unik\u00e1tn\u00ed kombinac\u00ed n\u011bkolika \u00fa\u010dinn\u00fdch l\u00e1tek.<\/li>\n
- Nen\u00ed k dispozici metoda na stanoven\u00ed obsahu doprovodn\u00e9 l\u00e1tky nebo zn\u00e1m\u00e9 ne\u010distoty.<\/li>\n
- <\/li>\n<\/ul>\n
Ve v\u011bt\u0161in\u011b p\u0159\u00edpad\u016f lze pou\u017e\u00edt techniku HPLC nebo UPLC. Na\u0161e laborato\u0159 je vybavena kapalinov\u00fdmi chromatografy Alliance 2690\/5 (Waters), Agilent 1100 a 1260 Infinity II (Agilent Technologies) a UHPLC syst\u00e9my Acquity UPLC (Waters) a 1290 Infinity (Agilent Technologies) p\u0159ev\u00e1\u017en\u011b s DAD-UV detekc\u00ed. \u00a0M\u00e1me k dispozici i ELSD 1290 Infinity II detektor (Agilent Technologies) a fluorescen\u010dn\u00ed detektor 474 (Waters).<\/p>\n
Pokud se HPLC\/UV metoda uk\u00e1\u017ee jako nedostate\u010dn\u011b selektivn\u00ed nebo m\u00e1lo citliv\u00e1 (nap\u0159. p\u0159i stopov\u00e9 anal\u00fdze), vyu\u017e\u00edv\u00e1me n\u00e1\u0161 LC\/MS syst\u00e9m vybaven\u00fd modern\u00edm hmotnostn\u00edm spektrometrem s line\u00e1rn\u00ed iontovou past\u00ed LTQ (Thermo-Finnigan).<\/p>\n
V n\u011bkter\u00fdch p\u0159\u00edpadech je st\u00e1le nejvhodn\u011bj\u0161\u00ed pou\u017e\u00edt techniku TLC, zejm\u00e9na v p\u0159\u00edpadech, kdy jsou sledovan\u00e9 l\u00e1tky obt\u00ed\u017en\u011b detekovateln\u00e9 pomoc\u00ed UV. Pro tento \u00fa\u010del jsme vybaveni TLC syst\u00e9mem od firmy Camag zahrnuj\u00edc\u00edm nan\u00e1\u0161ec\u00ed za\u0159\u00edzen\u00ed Linomat 4, v\u00fdvojovou komoru a detek\u010dn\u00ed komoru s digit\u00e1ln\u00ed videokamerou Reprostar 3.<\/p>\n
P\u0159i v\u00fdvoji metod na stanoven\u00ed t\u011bkav\u00fdch analyt\u016f vyu\u017e\u00edv\u00e1me GC\/FID nebo GC\/MS techniky, oboje v kombinaci bu\u010f s klasick\u00fdm kapalinov\u00fdm (s mo\u017enost\u00ed PTV) nebo statick\u00fdm \u010di dynamick\u00fdm headspace n\u00e1st\u0159ikem. Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me plynov\u00fd chromatograf 7890A\/5975C (Agilent Technologies) vybaven\u00fd autosamplerem CombiPAL (CTC Analytics) resp. 7697A (Agilent Technologies).<\/p>\n
Pro \u00fa\u010dely anal\u00fdzy vysoce pol\u00e1rn\u00edch organick\u00fdch l\u00e1tek nebo anorganick\u00fdch iont\u016f jsme vybaveni v\u00edce\u00fa\u010delov\u00fdm iontov\u00fdm chromatografem s mo\u017enost\u00ed vodivostn\u00ed nebo amperometrick\u00e9 detekce ICS3000 od firmy Dionex.<\/p>\n
Jako analytick\u00e1 podpora p\u0159edev\u0161\u00edm formula\u010dn\u00edho v\u00fdvoje, ale i pro pot\u0159eby n\u00e1sledn\u00e9ho testov\u00e1n\u00ed v komer\u010dn\u00ed f\u00e1zi prov\u00e1d\u00edme v\u00fdvoje disolu\u010dn\u00edch metod \u00a0– nej\u010dast\u011bji s vyu\u017eit\u00edm disolu\u010dn\u00edch syst\u00e9m\u016f s p\u00e1dly (zn\u00e1m\u00fdch jako USP apparatus II) \u010di ko\u0161\u00edky (USP apparatus I). K t\u011bmto \u00fa\u010del\u016fm m\u00e1me k dispozici syst\u00e9my VK7025 (VanKel) a 708DS (Agilent Technologies) vybaven\u00e9 automatick\u00fdm odb\u011brem vzork\u016f VK8000. \u00a0Nov\u011b m\u00e1me v portfoliu technik i disolu\u010dn\u00ed syst\u00e9m s pr\u016fto\u010dn\u00fdmi celami (USP apparatus IV) od firmy Sotax.<\/p>\n
D\u00e1le vyv\u00edj\u00edme metody pro stanoven\u00ed element\u00e1rn\u00edch ne\u010distot dle po\u017eadavk\u016f ICH guideline Q3D s pou\u017eit\u00edm ICP-MS syst\u00e9mu 7800 (Agilent) v\u010detn\u011b mineraliza\u010dn\u00edch procedur, kde pou\u017e\u00edv\u00e1me syst\u00e9my Microwave digestion system speedwave Xpert (Berghof).<\/p>\n
Krom\u011b t\u011bchto hlavn\u00edch \u010dinnost\u00ed je\u0161t\u011b zaji\u0161\u0165ujeme v\u00fdvoj metod pro stanoven\u00ed velikosti \u010d\u00e1stic s pou\u017eit\u00edm mikroskopie s obrazovou anal\u00fdzou a laserov\u00e9 difrakce (MasterSizer 3000, Malvern Instruments) d\u00e1le titra\u010dn\u00edch metod s p\u0159ev\u00e1\u017en\u011b potenciometrickou detekc\u00ed \u00a0(Titrino-Metrohm) a disolu\u010dn\u00edch metod (Varian, Hanson) s UV nebo HPLC koncovkou pro charakterizaci l\u00e9kov\u00fdch forem.<\/p>\n<\/div>
- Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/div><\/a><\/li><\/ul><\/div>\n
Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/h2>\n
Identifikace a ur\u010den\u00ed struktury ne\u010distoty je pom\u011brn\u011b \u010dast\u00fd \u00fakol, se kter\u00fdm se mus\u00edme vypo\u0159\u00e1dat. V\u0161echny nezn\u00e1m\u00e9 ne\u010distoty s obsahem vy\u0161\u0161\u00edm, ne\u017e dovoluje platn\u00e1 legislativa (zpravidla 0.1 %) jsou pro z\u00e1kazn\u00edka potenci\u00e1ln\u00ed komplikac\u00ed, proto\u017ee mohou vyvolat ne\u017e\u00e1douc\u00ed z\u00e1jem p\u0159i registra\u010dn\u00edm \u0159\u00edzen\u00ed.<\/p>\n
Znalost struktury nezn\u00e1m\u00e9 ne\u010distoty je potom \u010dasto kl\u00ed\u010dov\u00e1 p\u0159i odli\u0161en\u00ed ne\u010distot poch\u00e1zej\u00edc\u00edch z v\u00fdrobn\u00edho postupu od ne\u010distot vznikaj\u00edc\u00edch n\u00e1slednou degradac\u00ed fin\u00e1ln\u00edho produktu. Prvn\u011b jmenovan\u00e9 ne\u010distoty lze dostat pod kontrolu nap\u0159\u00edklad \u00fapravou v\u00fdrobn\u00edho postupu. P\u0159i znalosti struktury ne\u010distoty degrada\u010dn\u00edho p\u016fvodu lze zase c\u00edlen\u011b p\u0159ipravit jej\u00ed standard a na z\u00e1klad\u011b toxikologick\u00fdch dat, pop\u0159\u00edpad\u011b zv\u00fd\u0161it limit pro jej\u00ed obsah.<\/p>\n
V praxi pou\u017e\u00edv\u00e1me p\u0159i ur\u010dov\u00e1n\u00ed struktury l\u00e1tek hmotnostn\u00ed spektrometrii v tandemu bu\u010f s plynovou (GC-MS) nebo kapalinovou chromatografi\u00ed (LC-MS). Pro ur\u010dov\u00e1n\u00ed struktury t\u011bkav\u00fdch l\u00e1tek se n\u00e1m osv\u011bd\u010dilo pou\u017eit\u00ed GC-MS syst\u00e9mu s jednoduch\u00fdm kvadrup\u00f3lem, kter\u00fd nicm\u00e9n\u011b poskytuje p\u0159i pou\u017eit\u00ed EI ionizace dostate\u010dn\u00e9 mno\u017estv\u00ed informac\u00ed vedouc\u00edch k c\u00edlov\u00e9 struktu\u0159e. P\u0159i interpretaci spekter lze tak\u00e9 \u010dasto s \u00fasp\u011bchem vyu\u017e\u00edt i digit\u00e1ln\u00ed knihovnu hmotnostn\u00edch spekter (NIST).<\/p>\n
Dlouholet\u00e9 zku\u0161enosti uk\u00e1zaly, \u017ee pro identifikaci v\u011bt\u0161iny net\u011bkav\u00fdch organick\u00fdch ne\u010distot je nejlep\u0161\u00ed volbou pou\u017eit\u00ed LC-MS syst\u00e9mu s ESI nebo APCI ionizac\u00ed a iontovou past\u00ed. LC\/MS syst\u00e9m LTQ (Thermo-Finnigan), kter\u00fd k tomuto \u00fa\u010delu vyu\u017e\u00edv\u00e1me je vybaven\u00fd line\u00e1rn\u00ed iontovou past\u00ed, kter\u00e1 spojuje v\u00fdhody klasick\u00e9 iontov\u00e9 pasti s mo\u017enostmi MSn a citlivosti kvadrup\u00f3lu. V\u00fdhodou je p\u0159edev\u0161\u00edm vysok\u00e1 citlivost, rychlost sb\u011bru dat a d\u00edky ortogon\u00e1ln\u00ed konstrukci iontov\u00e9ho zdroje i odolnost v\u016f\u010di kontaminaci nap\u0159\u00edklad slo\u017ekami matrice nebo \u010d\u00e1ste\u010dn\u011b i net\u011bkav\u00fdm slo\u017ek\u00e1m v mobiln\u00ed f\u00e1zi.<\/p>\n
Pokud samotn\u00e9 LC\/MS nesta\u010d\u00ed, jsme schopni po\u017eadovan\u00e9 ne\u010distoty izolovat pomoc\u00ed preparativn\u00ed kapalinov\u00e9 chromatografie a zajistit nap\u0159\u00edklad m\u011b\u0159en\u00ed pot\u0159ebn\u00fdch NMR spekter, kter\u00e9 potom um\u00edme sami interpretovat.<\/p>\n
V n\u00e1vaznosti na identifikaci ne\u010distoty nap\u0159. pomoc\u00ed LC\/MS jsme schopni danou l\u00e1tku na p\u0159\u00e1n\u00ed z\u00e1kazn\u00edka chromatograficky izolovat ve v\u011bt\u0161\u00edm mno\u017estv\u00ed. M\u00edra \u00fasp\u011bchu z\u00e1le\u017e\u00ed na m\u00ed\u0159e separace k\u00fd\u017een\u00e9 komponenty od zbytku sm\u011bsi, ale p\u0159edev\u0161\u00edm na jej\u00edm obsahu v surov\u00e9m materi\u00e1lu. Pokud je obsah p\u0159\u00edli\u0161 n\u00edzk\u00fd, hled\u00e1me cesty k jeho nabohacen\u00ed a to bu\u010f vhodn\u011b zvolen\u00fdmi z\u00e1t\u011b\u017eov\u00fdmi podm\u00ednkami nebo p\u0159edseparac\u00ed.<\/p>\n
Izolace m\u016f\u017ee b\u00fdt u\u017eite\u010dn\u00e1 ve chv\u00edli, kdy bu\u010f nen\u00ed snadn\u00e9 l\u00e1tku c\u00edlen\u011b p\u0159ipravit, nebo je pot\u0159eba pro jej\u00ed identifikaci vyu\u017e\u00edt i jin\u00e9 techniky ne\u017e LC\/MS (nap\u0159\u00edklad NMR).<\/p>\n
Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me bu\u010f klasick\u00e9 sloupcov\u00e9 chromatografie nebo vysoko\u00fa\u010dinn\u00e9 separace na automatizovan\u00e9m semipreparativn\u00edm modul\u00e1rn\u00edm HPLC syst\u00e9mu Waters. Pomoc\u00ed t\u011bchto technik jsme schopni izolovat, v z\u00e1vislosti na koncentraci v surov\u00e9 sm\u011bsi a kvalit\u011b separace jednotliv\u00e9 komponenty v mno\u017estv\u00ed cca des\u00edtek a\u017e stovek mg.<\/p>\n<\/div>
- Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/div><\/a><\/li><\/ul><\/div>\n
Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/h2>\n
V n\u00e1vaznosti na p\u0159edchoz\u00ed bod t\u00fdkaj\u00edc\u00ed se ur\u010dov\u00e1n\u00ed struktur ne\u010distot \u010dasto vyvst\u00e1v\u00e1 pot\u0159eba z\u00edskat danou l\u00e1tku jako analytick\u00fd standard v dostate\u010dn\u00e9m mno\u017estv\u00ed tak, aby bylo mo\u017eno tuto ne\u010distotu rutinn\u011b stanovovat p\u0159\u00edslu\u0161n\u00fdmi metodami v produktu.<\/p>\n
Na\u0161\u00ed v\u00fdhodou je, \u017ee ji\u017e b\u011bhem procesu identifikace struktury \u010dasto vyvineme postupy, jimi\u017e lze danou l\u00e1tku c\u00edlen\u011b vyrobit synteticky p\u016fsoben\u00edm vhodn\u00fdch \u010dinidel nap\u0159. na \u00fa\u010dinnou l\u00e1tky nebo ji aspo\u0148 nabohatit.<\/p>\n
D\u00edky tomu dok\u00e1\u017eeme \u010dasto z\u00edskat po\u017eadovanou l\u00e1tku rychleji ne\u017e za pomoci klasick\u00fdch syntetick\u00fdch postup\u016f, kter\u00e9 ale ve vhodn\u00fdch p\u0159\u00edpadech vyu\u017e\u00edv\u00e1me tak\u00e9 \u010d\u00e1ste\u010dn\u011b ve spolupr\u00e1ci s extern\u00edmi syntetick\u00fdmi laborato\u0159emi.<\/p>\n
Dal\u0161\u00ed v\u00fdhodou je, \u017ee riziko neshody mezi p\u016fvodn\u011b navr\u017eenou strukturou ne\u010distoty a jej\u00ed skute\u010dnou strukturou neseme sami, co\u017e ve v\u00fdsledku m\u016f\u017ee p\u0159edstavovat nemal\u00e9 \u00faspory \u010dasu a pen\u011bz na stran\u011b z\u00e1kazn\u00edka.<\/p>\n
Samoz\u0159ejmost\u00ed je, \u017ee sami navrhneme a provedeme certifikaci dan\u00e9ho analytick\u00e9ho standardu v\u010detn\u011b pln\u00e9 charakterizace struktury, \u00a0stanoven\u00ed potence a vyd\u00e1n\u00ed analytick\u00e9ho certifik\u00e1tu.<\/p>\n<\/div>
- Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/div><\/a><\/li><\/ul><\/div>\n
Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/h2>\n
Sou\u010d\u00e1st\u00ed validace v\u011bt\u0161iny HPLC metod pro stanoven\u00ed obsahu ne\u010distot je tzv. degrada\u010dn\u00ed studie (FDS z angl. Forced Degradation Study). FDS je n\u00e1stroj pro hodnocen\u00ed analytick\u00fdch metod, kter\u00e9 aspiruj\u00ed na ozna\u010den\u00ed \u201estabilitn\u011b-indukuj\u00edc\u00ed\u201c. Principem FDS je vystaven\u00ed dan\u00e9 \u00fa\u010dinn\u00e9 l\u00e1tky resp. l\u00e9\u010div\u00e9ho p\u0159\u00edpravku (a p\u0159\u00edslu\u0161n\u00e9ho placeba) s\u00e9rii fyzik\u00e1ln\u00edch a chemick\u00fdch z\u00e1t\u011b\u017e\u00ed, jejich\u017e p\u016fsoben\u00edm se mohou v kr\u00e1tk\u00e9 dob\u011b generovat dosud nezn\u00e1m\u00e9 ne\u010distoty, kter\u00e9 se mohou potenci\u00e1ln\u011b vyskytnout ve fin\u00e1ln\u00edm produktu b\u011bhem skladov\u00e1n\u00ed. Fyzik\u00e1ln\u00ed a chemickou z\u00e1t\u011b\u017e\u00ed se rozum\u00ed zejm\u00e9na:<\/p>\n
\n- P\u016fsoben\u00ed tepla<\/li>\n
- Vystaven\u00ed sv\u011bteln\u00e9mu z\u00e1\u0159en\u00ed (UV\/VIS)<\/li>\n
- Kysel\u00e1, alkalick\u00e1 a oxida\u010dn\u00ed z\u00e1t\u011b\u017e<\/li>\n
- P\u016fsoben\u00ed zv\u00fd\u0161en\u00e9 teploty a vlhkosti prost\u0159ed\u00ed<\/li>\n<\/ul>\n
Zejm\u00e9na u chemick\u00fdch z\u00e1t\u011b\u017e\u00ed je pro volbu optim\u00e1ln\u00edch podm\u00ednek v\u00fdhodou dobr\u00e1 znalost chemick\u00e9ho chov\u00e1n\u00ed zkouman\u00e9 \u00fa\u010dinn\u00e9 l\u00e1tky. \u00a0P\u0159\u00edpadn\u00e9 interakce \u00fa\u010dinn\u00e9 l\u00e1tky s excipienty se zvl\u00e1\u0161\u0165 studuj\u00ed v r\u00e1mci tzv. kompatibilitn\u00edch studi\u00ed. \u00a0Zku\u0161enost uk\u00e1zala, \u017ee tento typ pr\u00e1ce je sp\u00ed\u0161e dom\u00e9nou R&D, kter\u00e9 prov\u00e1d\u00ed zrychlen\u00e9 stabilitn\u00ed, degrada\u010dn\u00ed a kompatibilitn\u00ed studie jako rutinn\u00ed sou\u010d\u00e1st v\u00fdvoje nov\u00fdch analytick\u00fdch metod, ale i jako podporu formula\u010dn\u00edho v\u00fdvoje dan\u00e9ho l\u00e9\u010div\u00e9ho p\u0159\u00edpravku.<\/p>\n<\/div>
- Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/div><\/a><\/li><\/ul><\/div>\n
Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/h2>\n
M\u00e1me bohat\u00e9 zku\u0161enosti s v\u00fdvojem metod pro stanoven\u00ed stopov\u00fdch mno\u017estv\u00ed sledovan\u00fdch ne\u010distot. Pro na\u0161e z\u00e1kazn\u00edky obvykle vyv\u00edj\u00edme metody pro stanoven\u00ed toxick\u00fdch ne\u010distot na hladin\u00e1ch n\u00e1sobn\u011b ni\u017e\u0161\u00edch, ne\u017e po\u017eaduj\u00ed p\u0159\u00edslu\u0161n\u00e9 regula\u010dn\u00ed autority. P\u0159esto\u017ee se nez\u0159\u00eddka jedn\u00e1 o analyty reaktivn\u00ed a \u010dasto v nep\u0159\u00edzniv\u00e9 kombinaci se \u0161patn\u011b rozpustnou nebo reaktivn\u00ed matric\u00ed, v\u017edy jsme zat\u00edm dos\u00e1hli po\u017eadovan\u00e9ho detek\u010dn\u00edho limitu.<\/p>\n
Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me nej\u010dast\u011bji techniku LC\/MS na syst\u00e9mech sest\u00e1vaj\u00edc\u00edch z HPLC 2690 \u010di UHPLC Acquity (oboj\u00ed Waters) a hmotov\u00e9ho spektrometru LTQ(Thermo-Finnigan) nebo GC\/MS na syst\u00e9mu 7890A\/5975C (Agilent Technologies). Na v\u0161ech t\u011bchto p\u0159\u00edstroj\u00edch b\u011b\u017en\u011b dosahujeme kvantifika\u010dn\u00ed limity v jednotk\u00e1ch ppm, co\u017e je pro farmaceutick\u00e9 \u00fa\u010dely v\u011bt\u0161inou zcela dostate\u010dn\u00e9.<\/p>\n
V p\u0159\u00edpad\u011b pot\u0159eby vyu\u017e\u00edv\u00e1me i jin\u00e9 p\u0159\u00edstrojov\u00e9 vybaven\u00ed spole\u010dnosti \u010d\u00edtaj\u00edc\u00ed n\u011bkolik LC\/MS syst\u00e9m\u016f vybaven\u00fdch hmotnostn\u00edmi i spektrometry s trojit\u00fdm kvadrup\u00f3lem \u010di HR-MS syst\u00e9mu OrbiTrap (Thermo).<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div>
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<\/span><\/div><\/div><\/div><\/span>MONITORING STUDI\u00cd<\/h4><\/span><\/div><\/div><\/div>Oversight of participant health and correctness of treatments during clinical studies.<\/p>\n<\/div><\/div><\/div>
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V\u00fdvoj analytick\u00fdch metod, analytika ne\u010distot, studie degradace, stopov\u00e9 anal\u00fdzy a dal\u0161\u00ed.
\nPomoc\u00ed na\u0161ich analytick\u00fdch znalost\u00ed a nejmodern\u011bj\u0161\u00edho vybaven\u00ed podporujeme klienty b\u011bhem v\u00fdvoje a registrace jejich l\u00e9k\u016f podle nejnov\u011bj\u0161\u00edch trend\u016f v analytick\u00e9 chemii.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
- V\u00fdvoj analytick\u00fdch metod<\/div><\/a><\/li>Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/div><\/a><\/li>Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/div><\/a><\/li>Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/div><\/a><\/li>Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/div><\/a><\/li><\/ul><\/div>
- V\u00fdvoj analytick\u00fdch metod<\/div><\/a><\/li><\/ul><\/div>\n
V\u00fdvoj analytick\u00fdch metod<\/h2>\n
Jako ka\u017ed\u00e1 \u00fasp\u011b\u0161n\u00e1 spole\u010dnost mus\u00edme b\u00fdt efektivn\u00ed, flexibiln\u00ed a modern\u00ed. P\u0159esn\u011b v tomto duchu pracuje i na\u0161e odd\u011blen\u00ed v\u00fdvoje a v\u00fdzkumu. Jsme kompaktn\u00ed a inovativn\u00ed t\u00fdm expert\u016f. P\u0159i sv\u00e9 pr\u00e1ci pou\u017e\u00edv\u00e1me modern\u00ed p\u0159\u00edstrojovou techniku a sledujeme nejnov\u011bj\u0161\u00ed trendy v oblasti analytick\u00e9 chemie, ale nezapom\u00edn\u00e1me ani na star\u00e9 dobr\u00e9 chemick\u00e9 postupy.<\/p>\n
V\u00fdvoj analytick\u00fdch metod
\n<\/strong>V\u00fdvoje a testov\u00e1n\u00ed nov\u00fdch analytick\u00fdch metod p\u0159edstavuje t\u011b\u017ei\u0161t\u011b na\u0161\u00ed \u010dinnosti. Nej\u010dast\u011bj\u0161\u00ed d\u016fvody pro v\u00fdvoj analytick\u00e9 metody, se kter\u00fdmi se v praxi setk\u00e1v\u00e1me, jsou n\u00e1sleduj\u00edc\u00ed:<\/p>\n- \n
- P\u0159i v\u00fdvoji nov\u00e9 (patentov\u011b nechr\u00e1n\u011bn\u00e9) syntetick\u00e9 cesty k \u00fa\u010dinn\u00e9 l\u00e1tce je pot\u0159eba sledovat reak\u010dn\u00ed konverze a profily ne\u010distot u meziprodukt\u016f i fin\u00e1ln\u00edho produktu.<\/li>\n
- Analytick\u00e1 metoda pro stanoven\u00ed \u010distoty nebo obsahu fin\u00e1ln\u00ed \u00fa\u010dinn\u00e9 l\u00e1tky popsan\u00e1 v p\u0159\u00edslu\u0161n\u00e9m l\u00e9kopise je zastaral\u00e1 nebo nespl\u0148uje po\u017eadavky z\u00e1kazn\u00edka.<\/li>\n
- Nen\u00ed k dispozici vhodn\u00e1 metoda na stanoven\u00ed \u010distoty nebo obsahu \u00fa\u010dinn\u00e9 l\u00e1tky v nov\u00e9m l\u00e9\u010div\u00e9m p\u0159\u00edpravku.<\/li>\n
- Fin\u00e1ln\u00ed l\u00e9\u010divo je unik\u00e1tn\u00ed kombinac\u00ed n\u011bkolika \u00fa\u010dinn\u00fdch l\u00e1tek.<\/li>\n
- Nen\u00ed k dispozici metoda na stanoven\u00ed obsahu doprovodn\u00e9 l\u00e1tky nebo zn\u00e1m\u00e9 ne\u010distoty.<\/li>\n
- <\/li>\n<\/ul>\n
Ve v\u011bt\u0161in\u011b p\u0159\u00edpad\u016f lze pou\u017e\u00edt techniku HPLC nebo UPLC. Na\u0161e laborato\u0159 je vybavena kapalinov\u00fdmi chromatografy Alliance 2690\/5 (Waters), Agilent 1100 a 1260 Infinity II (Agilent Technologies) a UHPLC syst\u00e9my Acquity UPLC (Waters) a 1290 Infinity (Agilent Technologies) p\u0159ev\u00e1\u017en\u011b s DAD-UV detekc\u00ed. \u00a0M\u00e1me k dispozici i ELSD 1290 Infinity II detektor (Agilent Technologies) a fluorescen\u010dn\u00ed detektor 474 (Waters).<\/p>\n
Pokud se HPLC\/UV metoda uk\u00e1\u017ee jako nedostate\u010dn\u011b selektivn\u00ed nebo m\u00e1lo citliv\u00e1 (nap\u0159. p\u0159i stopov\u00e9 anal\u00fdze), vyu\u017e\u00edv\u00e1me n\u00e1\u0161 LC\/MS syst\u00e9m vybaven\u00fd modern\u00edm hmotnostn\u00edm spektrometrem s line\u00e1rn\u00ed iontovou past\u00ed LTQ (Thermo-Finnigan).<\/p>\n
V n\u011bkter\u00fdch p\u0159\u00edpadech je st\u00e1le nejvhodn\u011bj\u0161\u00ed pou\u017e\u00edt techniku TLC, zejm\u00e9na v p\u0159\u00edpadech, kdy jsou sledovan\u00e9 l\u00e1tky obt\u00ed\u017en\u011b detekovateln\u00e9 pomoc\u00ed UV. Pro tento \u00fa\u010del jsme vybaveni TLC syst\u00e9mem od firmy Camag zahrnuj\u00edc\u00edm nan\u00e1\u0161ec\u00ed za\u0159\u00edzen\u00ed Linomat 4, v\u00fdvojovou komoru a detek\u010dn\u00ed komoru s digit\u00e1ln\u00ed videokamerou Reprostar 3.<\/p>\n
P\u0159i v\u00fdvoji metod na stanoven\u00ed t\u011bkav\u00fdch analyt\u016f vyu\u017e\u00edv\u00e1me GC\/FID nebo GC\/MS techniky, oboje v kombinaci bu\u010f s klasick\u00fdm kapalinov\u00fdm (s mo\u017enost\u00ed PTV) nebo statick\u00fdm \u010di dynamick\u00fdm headspace n\u00e1st\u0159ikem. Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me plynov\u00fd chromatograf 7890A\/5975C (Agilent Technologies) vybaven\u00fd autosamplerem CombiPAL (CTC Analytics) resp. 7697A (Agilent Technologies).<\/p>\n
Pro \u00fa\u010dely anal\u00fdzy vysoce pol\u00e1rn\u00edch organick\u00fdch l\u00e1tek nebo anorganick\u00fdch iont\u016f jsme vybaveni v\u00edce\u00fa\u010delov\u00fdm iontov\u00fdm chromatografem s mo\u017enost\u00ed vodivostn\u00ed nebo amperometrick\u00e9 detekce ICS3000 od firmy Dionex.<\/p>\n
Jako analytick\u00e1 podpora p\u0159edev\u0161\u00edm formula\u010dn\u00edho v\u00fdvoje, ale i pro pot\u0159eby n\u00e1sledn\u00e9ho testov\u00e1n\u00ed v komer\u010dn\u00ed f\u00e1zi prov\u00e1d\u00edme v\u00fdvoje disolu\u010dn\u00edch metod \u00a0– nej\u010dast\u011bji s vyu\u017eit\u00edm disolu\u010dn\u00edch syst\u00e9m\u016f s p\u00e1dly (zn\u00e1m\u00fdch jako USP apparatus II) \u010di ko\u0161\u00edky (USP apparatus I). K t\u011bmto \u00fa\u010del\u016fm m\u00e1me k dispozici syst\u00e9my VK7025 (VanKel) a 708DS (Agilent Technologies) vybaven\u00e9 automatick\u00fdm odb\u011brem vzork\u016f VK8000. \u00a0Nov\u011b m\u00e1me v portfoliu technik i disolu\u010dn\u00ed syst\u00e9m s pr\u016fto\u010dn\u00fdmi celami (USP apparatus IV) od firmy Sotax.<\/p>\n
D\u00e1le vyv\u00edj\u00edme metody pro stanoven\u00ed element\u00e1rn\u00edch ne\u010distot dle po\u017eadavk\u016f ICH guideline Q3D s pou\u017eit\u00edm ICP-MS syst\u00e9mu 7800 (Agilent) v\u010detn\u011b mineraliza\u010dn\u00edch procedur, kde pou\u017e\u00edv\u00e1me syst\u00e9my Microwave digestion system speedwave Xpert (Berghof).<\/p>\n
Krom\u011b t\u011bchto hlavn\u00edch \u010dinnost\u00ed je\u0161t\u011b zaji\u0161\u0165ujeme v\u00fdvoj metod pro stanoven\u00ed velikosti \u010d\u00e1stic s pou\u017eit\u00edm mikroskopie s obrazovou anal\u00fdzou a laserov\u00e9 difrakce (MasterSizer 3000, Malvern Instruments) d\u00e1le titra\u010dn\u00edch metod s p\u0159ev\u00e1\u017en\u011b potenciometrickou detekc\u00ed \u00a0(Titrino-Metrohm) a disolu\u010dn\u00edch metod (Varian, Hanson) s UV nebo HPLC koncovkou pro charakterizaci l\u00e9kov\u00fdch forem.<\/p>\n<\/div>
- Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/div><\/a><\/li><\/ul><\/div>\n
Ur\u010dov\u00e1n\u00ed struktur ne\u010distot a jejich izolace<\/h2>\n
Identifikace a ur\u010den\u00ed struktury ne\u010distoty je pom\u011brn\u011b \u010dast\u00fd \u00fakol, se kter\u00fdm se mus\u00edme vypo\u0159\u00e1dat. V\u0161echny nezn\u00e1m\u00e9 ne\u010distoty s obsahem vy\u0161\u0161\u00edm, ne\u017e dovoluje platn\u00e1 legislativa (zpravidla 0.1 %) jsou pro z\u00e1kazn\u00edka potenci\u00e1ln\u00ed komplikac\u00ed, proto\u017ee mohou vyvolat ne\u017e\u00e1douc\u00ed z\u00e1jem p\u0159i registra\u010dn\u00edm \u0159\u00edzen\u00ed.<\/p>\n
Znalost struktury nezn\u00e1m\u00e9 ne\u010distoty je potom \u010dasto kl\u00ed\u010dov\u00e1 p\u0159i odli\u0161en\u00ed ne\u010distot poch\u00e1zej\u00edc\u00edch z v\u00fdrobn\u00edho postupu od ne\u010distot vznikaj\u00edc\u00edch n\u00e1slednou degradac\u00ed fin\u00e1ln\u00edho produktu. Prvn\u011b jmenovan\u00e9 ne\u010distoty lze dostat pod kontrolu nap\u0159\u00edklad \u00fapravou v\u00fdrobn\u00edho postupu. P\u0159i znalosti struktury ne\u010distoty degrada\u010dn\u00edho p\u016fvodu lze zase c\u00edlen\u011b p\u0159ipravit jej\u00ed standard a na z\u00e1klad\u011b toxikologick\u00fdch dat, pop\u0159\u00edpad\u011b zv\u00fd\u0161it limit pro jej\u00ed obsah.<\/p>\n
V praxi pou\u017e\u00edv\u00e1me p\u0159i ur\u010dov\u00e1n\u00ed struktury l\u00e1tek hmotnostn\u00ed spektrometrii v tandemu bu\u010f s plynovou (GC-MS) nebo kapalinovou chromatografi\u00ed (LC-MS). Pro ur\u010dov\u00e1n\u00ed struktury t\u011bkav\u00fdch l\u00e1tek se n\u00e1m osv\u011bd\u010dilo pou\u017eit\u00ed GC-MS syst\u00e9mu s jednoduch\u00fdm kvadrup\u00f3lem, kter\u00fd nicm\u00e9n\u011b poskytuje p\u0159i pou\u017eit\u00ed EI ionizace dostate\u010dn\u00e9 mno\u017estv\u00ed informac\u00ed vedouc\u00edch k c\u00edlov\u00e9 struktu\u0159e. P\u0159i interpretaci spekter lze tak\u00e9 \u010dasto s \u00fasp\u011bchem vyu\u017e\u00edt i digit\u00e1ln\u00ed knihovnu hmotnostn\u00edch spekter (NIST).<\/p>\n
Dlouholet\u00e9 zku\u0161enosti uk\u00e1zaly, \u017ee pro identifikaci v\u011bt\u0161iny net\u011bkav\u00fdch organick\u00fdch ne\u010distot je nejlep\u0161\u00ed volbou pou\u017eit\u00ed LC-MS syst\u00e9mu s ESI nebo APCI ionizac\u00ed a iontovou past\u00ed. LC\/MS syst\u00e9m LTQ (Thermo-Finnigan), kter\u00fd k tomuto \u00fa\u010delu vyu\u017e\u00edv\u00e1me je vybaven\u00fd line\u00e1rn\u00ed iontovou past\u00ed, kter\u00e1 spojuje v\u00fdhody klasick\u00e9 iontov\u00e9 pasti s mo\u017enostmi MSn a citlivosti kvadrup\u00f3lu. V\u00fdhodou je p\u0159edev\u0161\u00edm vysok\u00e1 citlivost, rychlost sb\u011bru dat a d\u00edky ortogon\u00e1ln\u00ed konstrukci iontov\u00e9ho zdroje i odolnost v\u016f\u010di kontaminaci nap\u0159\u00edklad slo\u017ekami matrice nebo \u010d\u00e1ste\u010dn\u011b i net\u011bkav\u00fdm slo\u017ek\u00e1m v mobiln\u00ed f\u00e1zi.<\/p>\n
Pokud samotn\u00e9 LC\/MS nesta\u010d\u00ed, jsme schopni po\u017eadovan\u00e9 ne\u010distoty izolovat pomoc\u00ed preparativn\u00ed kapalinov\u00e9 chromatografie a zajistit nap\u0159\u00edklad m\u011b\u0159en\u00ed pot\u0159ebn\u00fdch NMR spekter, kter\u00e9 potom um\u00edme sami interpretovat.<\/p>\n
V n\u00e1vaznosti na identifikaci ne\u010distoty nap\u0159. pomoc\u00ed LC\/MS jsme schopni danou l\u00e1tku na p\u0159\u00e1n\u00ed z\u00e1kazn\u00edka chromatograficky izolovat ve v\u011bt\u0161\u00edm mno\u017estv\u00ed. M\u00edra \u00fasp\u011bchu z\u00e1le\u017e\u00ed na m\u00ed\u0159e separace k\u00fd\u017een\u00e9 komponenty od zbytku sm\u011bsi, ale p\u0159edev\u0161\u00edm na jej\u00edm obsahu v surov\u00e9m materi\u00e1lu. Pokud je obsah p\u0159\u00edli\u0161 n\u00edzk\u00fd, hled\u00e1me cesty k jeho nabohacen\u00ed a to bu\u010f vhodn\u011b zvolen\u00fdmi z\u00e1t\u011b\u017eov\u00fdmi podm\u00ednkami nebo p\u0159edseparac\u00ed.<\/p>\n
Izolace m\u016f\u017ee b\u00fdt u\u017eite\u010dn\u00e1 ve chv\u00edli, kdy bu\u010f nen\u00ed snadn\u00e9 l\u00e1tku c\u00edlen\u011b p\u0159ipravit, nebo je pot\u0159eba pro jej\u00ed identifikaci vyu\u017e\u00edt i jin\u00e9 techniky ne\u017e LC\/MS (nap\u0159\u00edklad NMR).<\/p>\n
Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me bu\u010f klasick\u00e9 sloupcov\u00e9 chromatografie nebo vysoko\u00fa\u010dinn\u00e9 separace na automatizovan\u00e9m semipreparativn\u00edm modul\u00e1rn\u00edm HPLC syst\u00e9mu Waters. Pomoc\u00ed t\u011bchto technik jsme schopni izolovat, v z\u00e1vislosti na koncentraci v surov\u00e9 sm\u011bsi a kvalit\u011b separace jednotliv\u00e9 komponenty v mno\u017estv\u00ed cca des\u00edtek a\u017e stovek mg.<\/p>\n<\/div>
- Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/div><\/a><\/li><\/ul><\/div>\n
Synt\u00e9za a certifikace referen\u010dn\u00edch materi\u00e1l\u016f<\/h2>\n
V n\u00e1vaznosti na p\u0159edchoz\u00ed bod t\u00fdkaj\u00edc\u00ed se ur\u010dov\u00e1n\u00ed struktur ne\u010distot \u010dasto vyvst\u00e1v\u00e1 pot\u0159eba z\u00edskat danou l\u00e1tku jako analytick\u00fd standard v dostate\u010dn\u00e9m mno\u017estv\u00ed tak, aby bylo mo\u017eno tuto ne\u010distotu rutinn\u011b stanovovat p\u0159\u00edslu\u0161n\u00fdmi metodami v produktu.<\/p>\n
Na\u0161\u00ed v\u00fdhodou je, \u017ee ji\u017e b\u011bhem procesu identifikace struktury \u010dasto vyvineme postupy, jimi\u017e lze danou l\u00e1tku c\u00edlen\u011b vyrobit synteticky p\u016fsoben\u00edm vhodn\u00fdch \u010dinidel nap\u0159. na \u00fa\u010dinnou l\u00e1tky nebo ji aspo\u0148 nabohatit.<\/p>\n
D\u00edky tomu dok\u00e1\u017eeme \u010dasto z\u00edskat po\u017eadovanou l\u00e1tku rychleji ne\u017e za pomoci klasick\u00fdch syntetick\u00fdch postup\u016f, kter\u00e9 ale ve vhodn\u00fdch p\u0159\u00edpadech vyu\u017e\u00edv\u00e1me tak\u00e9 \u010d\u00e1ste\u010dn\u011b ve spolupr\u00e1ci s extern\u00edmi syntetick\u00fdmi laborato\u0159emi.<\/p>\n
Dal\u0161\u00ed v\u00fdhodou je, \u017ee riziko neshody mezi p\u016fvodn\u011b navr\u017eenou strukturou ne\u010distoty a jej\u00ed skute\u010dnou strukturou neseme sami, co\u017e ve v\u00fdsledku m\u016f\u017ee p\u0159edstavovat nemal\u00e9 \u00faspory \u010dasu a pen\u011bz na stran\u011b z\u00e1kazn\u00edka.<\/p>\n
Samoz\u0159ejmost\u00ed je, \u017ee sami navrhneme a provedeme certifikaci dan\u00e9ho analytick\u00e9ho standardu v\u010detn\u011b pln\u00e9 charakterizace struktury, \u00a0stanoven\u00ed potence a vyd\u00e1n\u00ed analytick\u00e9ho certifik\u00e1tu.<\/p>\n<\/div>
- Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/div><\/a><\/li><\/ul><\/div>\n
Zrychlen\u00e9 stabilitn\u00ed a degrada\u010dn\u00ed studie<\/h2>\n
Sou\u010d\u00e1st\u00ed validace v\u011bt\u0161iny HPLC metod pro stanoven\u00ed obsahu ne\u010distot je tzv. degrada\u010dn\u00ed studie (FDS z angl. Forced Degradation Study). FDS je n\u00e1stroj pro hodnocen\u00ed analytick\u00fdch metod, kter\u00e9 aspiruj\u00ed na ozna\u010den\u00ed \u201estabilitn\u011b-indukuj\u00edc\u00ed\u201c. Principem FDS je vystaven\u00ed dan\u00e9 \u00fa\u010dinn\u00e9 l\u00e1tky resp. l\u00e9\u010div\u00e9ho p\u0159\u00edpravku (a p\u0159\u00edslu\u0161n\u00e9ho placeba) s\u00e9rii fyzik\u00e1ln\u00edch a chemick\u00fdch z\u00e1t\u011b\u017e\u00ed, jejich\u017e p\u016fsoben\u00edm se mohou v kr\u00e1tk\u00e9 dob\u011b generovat dosud nezn\u00e1m\u00e9 ne\u010distoty, kter\u00e9 se mohou potenci\u00e1ln\u011b vyskytnout ve fin\u00e1ln\u00edm produktu b\u011bhem skladov\u00e1n\u00ed. Fyzik\u00e1ln\u00ed a chemickou z\u00e1t\u011b\u017e\u00ed se rozum\u00ed zejm\u00e9na:<\/p>\n
- \n
- P\u016fsoben\u00ed tepla<\/li>\n
- Vystaven\u00ed sv\u011bteln\u00e9mu z\u00e1\u0159en\u00ed (UV\/VIS)<\/li>\n
- Kysel\u00e1, alkalick\u00e1 a oxida\u010dn\u00ed z\u00e1t\u011b\u017e<\/li>\n
- P\u016fsoben\u00ed zv\u00fd\u0161en\u00e9 teploty a vlhkosti prost\u0159ed\u00ed<\/li>\n<\/ul>\n
Zejm\u00e9na u chemick\u00fdch z\u00e1t\u011b\u017e\u00ed je pro volbu optim\u00e1ln\u00edch podm\u00ednek v\u00fdhodou dobr\u00e1 znalost chemick\u00e9ho chov\u00e1n\u00ed zkouman\u00e9 \u00fa\u010dinn\u00e9 l\u00e1tky. \u00a0P\u0159\u00edpadn\u00e9 interakce \u00fa\u010dinn\u00e9 l\u00e1tky s excipienty se zvl\u00e1\u0161\u0165 studuj\u00ed v r\u00e1mci tzv. kompatibilitn\u00edch studi\u00ed. \u00a0Zku\u0161enost uk\u00e1zala, \u017ee tento typ pr\u00e1ce je sp\u00ed\u0161e dom\u00e9nou R&D, kter\u00e9 prov\u00e1d\u00ed zrychlen\u00e9 stabilitn\u00ed, degrada\u010dn\u00ed a kompatibilitn\u00ed studie jako rutinn\u00ed sou\u010d\u00e1st v\u00fdvoje nov\u00fdch analytick\u00fdch metod, ale i jako podporu formula\u010dn\u00edho v\u00fdvoje dan\u00e9ho l\u00e9\u010div\u00e9ho p\u0159\u00edpravku.<\/p>\n<\/div>
- Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/div><\/a><\/li><\/ul><\/div>\n
Stopov\u00e1 anal\u00fdza pomoc\u00ed GC\/MS a LC\/MS<\/h2>\n
M\u00e1me bohat\u00e9 zku\u0161enosti s v\u00fdvojem metod pro stanoven\u00ed stopov\u00fdch mno\u017estv\u00ed sledovan\u00fdch ne\u010distot. Pro na\u0161e z\u00e1kazn\u00edky obvykle vyv\u00edj\u00edme metody pro stanoven\u00ed toxick\u00fdch ne\u010distot na hladin\u00e1ch n\u00e1sobn\u011b ni\u017e\u0161\u00edch, ne\u017e po\u017eaduj\u00ed p\u0159\u00edslu\u0161n\u00e9 regula\u010dn\u00ed autority. P\u0159esto\u017ee se nez\u0159\u00eddka jedn\u00e1 o analyty reaktivn\u00ed a \u010dasto v nep\u0159\u00edzniv\u00e9 kombinaci se \u0161patn\u011b rozpustnou nebo reaktivn\u00ed matric\u00ed, v\u017edy jsme zat\u00edm dos\u00e1hli po\u017eadovan\u00e9ho detek\u010dn\u00edho limitu.<\/p>\n
Pro tyto \u00fa\u010dely vyu\u017e\u00edv\u00e1me nej\u010dast\u011bji techniku LC\/MS na syst\u00e9mech sest\u00e1vaj\u00edc\u00edch z HPLC 2690 \u010di UHPLC Acquity (oboj\u00ed Waters) a hmotov\u00e9ho spektrometru LTQ(Thermo-Finnigan) nebo GC\/MS na syst\u00e9mu 7890A\/5975C (Agilent Technologies). Na v\u0161ech t\u011bchto p\u0159\u00edstroj\u00edch b\u011b\u017en\u011b dosahujeme kvantifika\u010dn\u00ed limity v jednotk\u00e1ch ppm, co\u017e je pro farmaceutick\u00e9 \u00fa\u010dely v\u011bt\u0161inou zcela dostate\u010dn\u00e9.<\/p>\n
V p\u0159\u00edpad\u011b pot\u0159eby vyu\u017e\u00edv\u00e1me i jin\u00e9 p\u0159\u00edstrojov\u00e9 vybaven\u00ed spole\u010dnosti \u010d\u00edtaj\u00edc\u00ed n\u011bkolik LC\/MS syst\u00e9m\u016f vybaven\u00fdch hmotnostn\u00edmi i spektrometry s trojit\u00fdm kvadrup\u00f3lem \u010di HR-MS syst\u00e9mu OrbiTrap (Thermo).<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div>
<\/div><\/div><\/span>Additional Services<\/h2><\/span>
<\/div><\/div><\/div><\/div><\/div><\/span><\/div><\/div><\/div><\/span>NITROSAMINES ANALYSIS<\/h4><\/span>
<\/div><\/div><\/div>Based on isotopically labeled standards, our customizable in-house detection methods are available immediately.<\/p>\n<\/div>
<\/div><\/div><\/span>More Info <\/i><\/a><\/h1><\/span>
<\/div><\/div><\/div><\/div><\/div><\/span><\/div><\/div><\/div><\/span>MONITORING STUDI\u00cd<\/h4><\/span>
<\/div><\/div><\/div>Oversight of participant health and correctness of treatments during clinical studies.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/span>FARMAKOVIGILANCE<\/h4><\/span>
<\/div><\/div><\/div>Monitoring of daily routine to detect unrecognized adverse events, plus assess and ensure drug safety.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/span>AUDIT MODULU 3<\/h4><\/span>
<\/div><\/div><\/div>Thorough dossier M3 data audit to ensure consistency and compliance with regulatory requirements.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/span>KOMPILACE IMPD<\/h4><\/span>
<\/div><\/div><\/div>As an EU based company we are well-placed to help create & develop your IMPD.<\/p>\n<\/div><\/div><\/div>
<\/div><\/div><\/span>Ot\u00e1zky na obchodn\u00ed t\u00fdm?<\/p><\/span>
<\/div><\/div><\/div>Our Sales team is ready to help: sales@quinta.cz<\/a><\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>\n