SK562006A3 - A method for determining the content of carbetopendecin bromide by liquid chromatography - Google Patents
A method for determining the content of carbetopendecin bromide by liquid chromatography Download PDFInfo
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- SK562006A3 SK562006A3 SK56-2006A SK562006A SK562006A3 SK 562006 A3 SK562006 A3 SK 562006A3 SK 562006 A SK562006 A SK 562006A SK 562006 A3 SK562006 A3 SK 562006A3
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- 238000000034 method Methods 0.000 title claims description 26
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 title description 26
- 238000004811 liquid chromatography Methods 0.000 title description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- FXQJFHYFOGHZTB-UHFFFAOYSA-M carbethopendecinium bromide Chemical compound [Br-].CCCCCCCCCCCCCCC([N+](C)(C)C)C(=O)OCC FXQJFHYFOGHZTB-UHFFFAOYSA-M 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- 238000010828 elution Methods 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 229910000077 silane Inorganic materials 0.000 claims description 3
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 150000001343 alkyl silanes Chemical class 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000004007 reversed phase HPLC Methods 0.000 claims 1
- 239000000523 sample Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 7
- 238000003556 assay Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- -1 compound [1- (ethoxycarbonyl) pentadecyl] trimethylammonium bromide Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003889 eye drop Substances 0.000 description 4
- ACQYZSFXPXXIHL-UHFFFAOYSA-N 2-phenylmethoxycarbonyl-3,4-dihydro-1h-isoquinoline-1-carboxylic acid Chemical compound C1CC2=CC=CC=C2C(C(=O)O)N1C(=O)OCC1=CC=CC=C1 ACQYZSFXPXXIHL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000031973 Conjunctivitis infective Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 201000007032 bacterial conjunctivitis Diseases 0.000 description 2
- 208000010217 blepharitis Diseases 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- UEHUZQKLOWYOMO-UHFFFAOYSA-N diethylazanium;acetate Chemical compound CC(O)=O.CCNCC UEHUZQKLOWYOMO-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- VWQMDHRZIPQGJQ-UHFFFAOYSA-N n-ethylethanamine;formic acid Chemical compound [O-]C=O.CC[NH2+]CC VWQMDHRZIPQGJQ-UHFFFAOYSA-N 0.000 description 1
- IVQXXLUOYFEVCI-UHFFFAOYSA-N n-ethylethanamine;propanoic acid Chemical compound CC[NH2+]CC.CCC([O-])=O IVQXXLUOYFEVCI-UHFFFAOYSA-N 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 201000003826 superficial keratitis Diseases 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000005496 tempering Methods 0.000 description 1
- QBVXKDJEZKEASM-UHFFFAOYSA-M tetraoctylammonium bromide Chemical compound [Br-].CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC QBVXKDJEZKEASM-UHFFFAOYSA-M 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B61—RAILWAYS
- B61F—RAIL VEHICLE SUSPENSIONS, e.g. UNDERFRAMES, BOGIES OR ARRANGEMENTS OF WHEEL AXLES; RAIL VEHICLES FOR USE ON TRACKS OF DIFFERENT WIDTH; PREVENTING DERAILING OF RAIL VEHICLES; WHEEL GUARDS, OBSTRUCTION REMOVERS OR THE LIKE FOR RAIL VEHICLES
- B61F5/00—Constructional details of bogies; Connections between bogies and vehicle underframes; Arrangements or devices for adjusting or allowing self-adjustment of wheel axles or bogies when rounding curves
- B61F5/26—Mounting or securing axle-boxes in vehicle or bogie underframes
- B61F5/30—Axle-boxes mounted for movement under spring control in vehicle or bogie underframes
- B61F5/307—Axle-boxes mounted for movement under spring control in vehicle or bogie underframes incorporating fluid springs
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- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Vehicle Body Suspensions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
Oblasť technikyTechnical field
Vynález sa týka spôsobu stanovenia obsahu karbetopendecínium bromidu metódou kvapalinovej chromatografie vo farmaceutických prípravkoch. Stanovenie je možno použiť pri kontrole substancie a alebo jej obsahu v kvapalných, pevných alebo plynných liekových formách.The invention relates to a method for determining the content of carbetopendecin bromide by a liquid chromatography method in pharmaceutical preparations. The assay can be used to control the substance and / or its content in liquid, solid or gaseous dosage forms.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Zlúčenina [1-(etoxykarbonyl)pentadecyl]trimetylammonium bromid, karbetopendecínium bromid (Synonymum. Carbethopendecinii bromidum, Septonex, Carbethopendecinium bromatum) vzorca I,The compound [1- (ethoxycarbonyl) pentadecyl] trimethylammonium bromide, carbetopendecinium bromide (Synonym. Carbethopendecinii bromidum, Septonex, Carbethopendecinium bromatum) of formula I,
C2H5OCO-CH-N+(CH3)3 Br'C2H5OCO-CH-N + (CH 3) 3 Br
I (CH2)13—— ch3 (i, je antiseptikum zo skupiny kvartérnych amóniových solí s bakteriostatickým účinkom.I (CH 2 ) 13 -CH 3 (i ) is an antiseptic of the family of quaternary ammonium salts with bacteriostatic activity.
Používa sa ako dermatologikum a dezinfektant. Ako aktívna komponenta predovšetkým v prípravkoch na dezinfekciu kože, dezinfekciu povrchových poranení, ale aj dekontamináciu obuvi a rukavíc pri mykózach. Ďalej sa používa k liečbe drobných prejavov kožného hnisania prejavujúcich sa sčervenaním, mokvaním, a to i pri výskyte vo vlasatej časti hlavy.It is used as a dermatological and disinfectant. As an active component especially in preparations for skin disinfection, disinfection of surface injuries, but also decontamination of shoes and gloves in mycoses. It is also used for the treatment of minor manifestations of skin festering with redness, swelling, even in the scalp.
Používa sa ako zložka sprayov deodorantov s antiseptickým účinkom proti baktériám, vírusom a plesniam a alebo vo veterinárnej medicíne. Je tiež pomocnou látkou v rôznych mastiach, zásypoch a géloch. Sú napr. známe dentálne výrobky ako zubné pasty, gély lokálnych anestetík a antiseptík, očné instilácie napr. masť pre liečbu akútnej i chronickej nehnisavej konjunktivitidy alebo blefaritidy, stavy po extrakcii cudzích teliesok z rohovky, alebo kvapky pre akútnu i chronickú nehnisavú konjunktivitidu alebo blefaritidu, nehnisavú povrchovú keratitidu.It is used as a component of deodorant sprays with antiseptic action against bacteria, viruses and fungi or in veterinary medicine. It is also an adjuvant in various ointments, dusting powders and gels. They are eg. known dental products such as toothpastes, gels of local anesthetics and antiseptics, eye instillations e.g. ointment for the treatment of both acute and chronic non-purulent conjunctivitis or blepharitis, conditions following the extraction of foreign bodies from the cornea, or drops for both acute and chronic non-purulent conjunctivitis or blepharitis, non-purulent superficial keratitis.
Doteraz používaná metóda stanovenia obsahu a čistoty karbetopendecinium bromidu opísaná napr. v liekopisnom článku (Český lékopis V diel, str. 5449, 2002) je limitovaná jeho koncentráciou najmä pri stanovení v nízkych koncentráciách. Titračné stanovenia taktiež neumožňujú rozlíšenie medzi degradačnými a „in-process nečistotami a výber optimálnej metódy pre stanovenie týchto je rozhodujúci. (S. Ahuja ed. in: Chromatography of Pharmaceuticals. ACS Symposium Šerieš 512, 1992. AChS, Washington.)The method used to determine the content and purity of carbetopendecinium bromide as described in e.g. in a pharmacopoeial article (Czech Pharmacopoeia V vol, p. 5449, 2002) is limited by its concentration, especially when determined at low concentrations. Also, titration assays do not allow a distinction between degradation and "in-process impurities" and the choice of the optimal method for determining these is critical. (S. Ahuja ed. In: Chromatography of Pharmaceuticals. ACS Symposium Seriah 512, 1992. AChS, Washington.)
Z hľadiska bezpečnosti, regulačné orgány všeobecne vyžadujú výrobnú špecifikáciu s deklarovaným obsahom použitých látok. Ďalej stabilitné testy vyžadujú potvrdenie, že prítomné látky sa v ich priebehu nezmenili. Je dôležité doložiť, že pred aplikáciou sa produkt neodlišuje svojím zložením od schválenej špecifikácie. Stabilita látky je zásadne ovplyvňovaná množstvom nečistôt v nej obsiahnutých, či už majú pôvod v nedokonalom vyčistení pri výrobe alebo vznikajú intermolekulárnymi reakciami viaczložkových sústav pri skladovaní. Z uvedeného vidieť, že stanovenie pri nízkych koncentráciách je klúčové.From a safety point of view, regulators generally require a manufacturing specification with a declared content of substances used. Furthermore, stability tests require confirmation that the substances present have not changed during their course. It is important to demonstrate that the product does not differ in its composition from the approved specification before application. The stability of the substance is fundamentally influenced by the amount of impurities contained therein, whether they originate from incomplete purification during manufacture or arise from intermolecular reactions of multi-component systems during storage. It can be seen from the above that the determination at low concentrations is crucial.
Pre stanovenie obsahu karbetopendecinium bromidu napr. v očných instiláciách sa používa UV spektroskopia, je však limitované kôpri viaczložkovom stanovení alebo vyžaduje opakovanú prípravu vzoriek. Nevýhodou je použiteľnosť len na vysoko koncentrované vzorky prípravkov.To determine the carbetopendecinium bromide content e.g. ophthalmic instillation uses UV spectroscopy, but is limited to multi-component assays or requires repeated sample preparation. The disadvantage is the applicability only to highly concentrated sample preparations.
Ďalšou ťažkosťou pri uskutočňovaní postupu stanovenia podía doterajších postupov je ich prácnosť, nešpecifickosť a veiká spotreba času pri príprave vzorky a stanovení. Robustné a spoľahlivé analytické stanovenie substancie karbetopendecínium hromid a aj jeho liekových foriem má potvrdiť alebo vylúčiť, že je v limitoch povolených pre farmaceutickú kvalitu produktov.Another difficulty in carrying out the assay procedure of the prior art is their laboriousness, non-specificity, and great time consumption in sample preparation and assays. The robust and reliable analytical determination of the substance carbetopendecinium piles and its pharmaceutical forms should confirm or exclude that it is within the limits permitted for the pharmaceutical quality of the products.
Zvláštny význam má stanovenie v rôznych koncentráciách v rozličných produktoch a bolo teda potrebné navrhnúť všeobecnú metódu stanovenia karbetopendecínium bromidu v rôznych zmesiach.Of particular importance is the determination at different concentrations in different products and it was therefore necessary to devise a general method for the determination of carbetopendecin bromide in various mixtures.
Napriek veľkej aplikácii kvapalinovej chromatografie nie sú publikované práce zaoberajúce sa separáciou karbetopendecínium bromidu metódou kvapalinovej chromatografie v liečivých prípravkoch. Nie sú opísané ani práce zaoberajúce sa stanovením obsahu a čistoty karbetopendecínium bromidu metódou kvapalinovej chromatografie.Despite the large application of liquid chromatography, there is no published work on the separation of carbetopendecin bromide by the liquid chromatography method in medicinal products. There is also no description of the work on the determination and purity of carbetopendecinium bromide by the liquid chromatography method.
Nedostatky doteraz používaných metód teda odstraňuje spôsob stanovenia podľa vynálezu.The drawbacks of the methods used hitherto are thus eliminated by the method of the invention.
Bolo zistené, že karbetopendecínium bromid je možné stanoviť postupom podľa vynálezu metódou vysokoúčinnej kvapalinovej chromatografie na základe separácie na reverznej fáze napr. alkyl-, fenyl-, kyanoalkyl- alebo aminoalkylsilánového typu v prítomnosti tetralkylammóniových solí.It has been found that carbetopendecin bromide can be determined by the process of the invention by high performance liquid chromatography based on reverse phase separation e.g. alkyl-, phenyl-, cyanoalkyl- or aminoalkylsilane type in the presence of tetralkylammonium salts.
Vynález sa teda týka spôsobu stanovenia obsahu a čistoty alkylammoniových zlúčenín metódou kvapalinovej chromatografie vo farmaceutických prípravkoch. Stanovenie je možné použiť pri *9 kontrole samotnej substancie a alebo jej obsahu v kvapalných, pevných alebo plynných liekových formách.Thus, the invention relates to a method for determining the content and purity of alkylammonium compounds by liquid chromatography method in pharmaceutical preparations. The assay can be used to control the substance itself or its content in liquid, solid or gaseous dosage forms.
Podstata vynálezuSUMMARY OF THE INVENTION
Podstatou vynálezu je spôsob stanovenia obsahu karbetopendecínium bromidu všeobecného vzorce I, vyznačujúci sa tým, že sa stanovenie vykoná metódou vysokoúčinnej kvapalinovej chromatografie na reverznej fáze alkyl-, fenylalkyl-, kyanoalkyl- alebo aminoalkyl silánového typu v prítomnosti tetralkylammoniových soli (všeobecného vzorca II, nR4N+X (II, kde X je skupina OH', Cl, HSO4, H2PO4' a R značí Cl až C8 alkyl elúciou s mobilnou fázou 5-30% organickej s vodou miešatelnej zložky a 95-70% vodnej zložky s výhodou kombinované s gradientom a použije sa chromatografická kolóna s priemerom častíc 2.5 až 5mikrometrov pri teplote kolóny 2 až 50°C, pričom prietok mobilnej fázy je 0.2 - 2.0 mL/min s detekciou pri vlnovej dĺžke 210 až 220 nm a dávkovaní 5-100 mikro L.The invention relates to a method for determination of karbetopendecínium bromide of the formula I, characterized in that the determination carried out by high performance liquid chromatography on a reverse phase alkyl, phenylalkyl, or kyanoalkyl- aminoalkyl silane in the presence of type tetralkylammoniových of (formula II, n R 4 N + X (II, where X is OH ', Cl, HSO 4 , H 2 PO 4 ' and R is C 1 to C 8 alkyl eluting with a mobile phase of 5-30% organic water-miscible component and 95-70% aqueous component preferably combined with a gradient and using a chromatography column with a particle diameter of 2.5 to 5 microns at a column temperature of 2 to 50 ° C, the mobile phase flow rate being 0.2-2.0 mL / min with detection at 210-220 nm and dosing 5-100 mikro L.
Tetralkylammoniové soli všeobecného vzorca II sa používajú na prípravu vodnej zložky mobilnej fázy a alebo sú rozpustené v rozpúšťadle použitom na prípravu roztoku vzorku látky I. Látky uvedeného typu sú komerčne dostupné.The tetralkylammonium salts of the formula II are used for the preparation of the aqueous component of the mobile phase or are dissolved in the solvent used for the preparation of the sample solution of the substance I. Substances of the said type are commercially available.
Ako stacionárna fáza pre separáciu sa použijú chemicky modifikované silikagél reverzné fázy alkylsilánového typu, napr. alkyl-, fenylalkyl-, kyanoalkyl- alebo aminoalkyl silán. Tieto typy kolón sú dostatočne známe. Bežne používané sú kolóny napr. Luna C8, Luna C18, Luna Phenyl-Hexyl, Purospher Star NH2.As the stationary phase for the separation, chemically modified silica gel alkylsilane type reverse phases, e.g. alkyl-, phenylalkyl-, cyanoalkyl- or aminoalkyl silane. These types of columns are well known. Commonly used columns are e.g. Luna C8, Luna C18, Phenyl-Hexyl Luna, Purospher Star NH2.
Separácia sa uskutočňuje pri teplotách od 2°C do teploty 50 °C s výhodou pri laboratórnej teplote.The separation is carried out at temperatures from 2 ° C to 50 ° C, preferably at room temperature.
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Mobilná fáza je zložená z 5-30% vodou miešatelnej organickej zložky a 95-70% vodnej zložky. Ako s vodou miešateľné rozpúšťadlá sa používa metanol, etanol, acetonitril. V závislosti na type analytu sa s výhodou separácia kombinuje s gradientovou elúciou. Podmienky použitého gradientu sú závislé od zloženia vzorky a závisia od prípadných zložiek prípravku.The mobile phase consists of 5-30% water-miscible organic component and 95-70% aqueous component. Methanol, ethanol, acetonitrile are used as water-miscible solvents. Depending on the type of analyte, the separation is preferably combined with a gradient elution. The conditions of the gradient used depend on the composition of the sample and depend on any components of the formulation.
Väčšina separácií sa uskutočňuje pri laboratórnej teplote, ale teplota kolóny môže byť upravená pre dosiahnutie vyššej účinnosti v závislosti na zložení vzorku prípravku. V priebehu analýzy však musí byť udržiavaná konštantná teplota mobilnej fázy a kolóny. Uvedené je dôležité pri príprave niektorých typov vzoriek ako masť alebo gél.Most separations are carried out at room temperature, but the column temperature can be adjusted to achieve higher efficiency depending on the composition of the formulation sample. However, the mobile phase and column temperature must be kept constant during the analysis. This is important in the preparation of some types of samples such as ointment or gel.
Hodnota pH je podmienená vlastnosťami chromatografovaného materiálu ale všeobecne sa pohybuje od 2 do 7. Výhodné je uskutočniť separáciu s prídavkom tlmivého roztoku k mobilnej fáze ako napríklad kyselina octová - diethylamín, kyselina propiónová - diethylamin, kyselina mravenčí - diethylamín, je možno použiť i iné amíny ako napr. trietylamín alebo amoniak a jeho soli. Je možné priamo použiť aj komerčne dostupné činidlá ako soli kyseliny octovej, fosforečnej alebo chloristej.The pH is determined by the properties of the chromatographed material but generally ranges from 2 to 7. It is preferred to carry out the separation with the addition of a buffer to the mobile phase such as acetic acid - diethylamine, propionic acid - diethylamine, formic acid - diethylamine. for example. triethylamine or ammonia and salts thereof. Commercially available reagents such as acetic, phosphoric or perchloric acid salts may also be used directly.
Pri použití hore uvedených mobilných fáz a chromatografických podmienok nedochádza k nežiaducej kvalitatívnej zmene píkov separovaných látok v priebehu chromatografického procesu (tvar píkov zostáva symetrický a reprodukovateľný) . Je zrejmé, že je možné vypočítať obsah stanovovaného karbetopendecínium bromidu pomocou kalibračných kriviek získaných s kalibračnými štandardmi.Using the above mobile phases and chromatographic conditions, there is no undesirable qualitative change in the peaks of the separated substances during the chromatographic process (the shape of the peaks remains symmetrical and reproducible). Obviously, it is possible to calculate the content of the determined carbetopendecin bromide using calibration curves obtained with calibration standards.
Ako detektor možno použiť detekciu spektrofotometrom s diódovým polom ale i iný detektor.As a detector can be used detection with a diode array spectrophotometer but also another detector.
Na obrázku 1 je chromatografický záznam vzorky gélu s obsahom karbetopendecínium bromidu. Vzorka gélu (cca 2,5 g/ 50 ml, faktor asymetrie pre pík karbetopendecínium bromidu je 1,36, rozlíšenie medzi píkom prislúchajúcim karbetopendecínium bromidu a zložkou placeba je 2,7)Figure 1 is a chromatographic record of a gel sample containing carbetopendecin bromide. Gel sample (approx. 2.5 g / 50 ml, asymmetry factor for carbetopendecin bromide peak is 1.36, resolution between the carbetopendecin bromide peak and placebo component is 2.7)
Na obrázku 2 je chromatografický záznam substancie karbetopendecínium bromidu(cca 50 mg/ 50 ml, faktor asymetrie pre pík karbetopendecínium bromidu je 1,17)Figure 2 shows the chromatographic record of the substance carbetopendecin bromide (about 50 mg / 50 ml, the asymmetry factor for the carbetopendecin bromide peak is 1.17)
Na obrázku 3 je chromatografický záznam vzorky očnej instilácie s obsahom karbetopendecínium bromidu (cca 5 ml/ 10 ml, faktor asymetrie pre pík karbetopendecínium bromidu je 1,21)Figure 3 is a chromatographic record of an eye instillation sample containing carbetopendecin bromide (about 5 ml / 10 ml, asymmetry factor for the carbetopendecin bromide peak is 1.21)
Na obrázku 4 je chromatografický záznam vzorky aerodisperzie s obsahom karbetopendecínium bromidu (cca 1 ml/ 50 ml, faktor asymetrie pre pík karbetopendecínium bromidu je 1,44)Figure 4 is a chromatographic record of an aerodispersion sample containing carbetopendecin bromide (about 1 ml / 50 ml, the asymmetry factor for the carbetopendecin bromide peak is 1.44)
Predkladaný vynález poskytuje spolahlivý spôsob stanovenia metódou kvapalinovej chromatografie. Vynález je ilustrovaný v nasledujúcich príkladoch uskutočnenia bez toho, aby sa na nich obmedzoval.The present invention provides a reliable method for determination by liquid chromatography method. The invention is illustrated by the following non-limiting Examples.
Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION
Príklad 1Example 1
Stanovenie obsahu karbetopendecínium bromidu v gélyDetermination of carbetopendecinium bromide content in gels
Navážilo sa 2,500 g vzorky liečiva vo forme gélu do 50 ml odmernej banky, pridalo sa 15 ml rozpúšťacieho roztoku (metanol + voda (1:10, v/v)) a 10 min. sa trepalo vo vodnom kúpeli pri 30°C. Pridalo sa ďalších 15 ml rozpúšťacieho roztoku (metanol + voda (1:10, v/v)) a opäť sa 10 min. trepalo vo vodnom kúpeli pri 30°C. Po temperácii a ustálení sa doplnil roztok v odmernej banke po značku rozpúšťacím roztokom. Pre analýzu sa použila kolóna C18 (250x4,6mm, 5pm), mobilná fáza :A 2.500 g sample of the drug as a gel was weighed into a 50 ml volumetric flask, 15 ml of a solution solution (methanol + water (1:10, v / v)) was added and 10 min. was shaken in a water bath at 30 ° C. An additional 15 mL of a solvent solution (methanol + water (1:10, v / v)) was added and again for 10 min. shake in a water bath at 30 ° C. After tempering and stabilization, the solution in the volumetric flask was made up to the mark with the solvent solution. For analysis, a C18 column (250x4.6mm, 5pm) was used, mobile phase:
KVKV
20% acetonitril, 80% roztok tetrabutylammonium dihydrogen fosfátu (c= lg/1), prietok : 1,0 ml/min., detekcia : UV 210 nm, dávkovaný objem : 20 μΐ, doba analýzy : 25 min., teplota 22°C. Chromatogram na obr. 1 ilustruje separáciu jednotlivých zložiek prípravku a karbetopendecínium bromidu. Stanovilo sa 2mg karbetopendecínium bromidu na lg gélu.20% acetonitrile, 80% tetrabutylammonium dihydrogen phosphate solution (c = 1g / l), flow rate: 1.0 ml / min, detection: UV 210 nm, dosing volume: 20 μΐ, analysis time: 25 min, temperature 22 ° C. The chromatogram in FIG. 1 illustrates the separation of the individual components of the formulation and carbetopendecin bromide. 2mg of carbetopendecin bromide per 1g of gel was determined.
Príklad 2Example 2
Určenie zloženia vzorky karbetopendecínium bromiduDetermination of sample composition of carbetopendecin bromide
Navážilo sa 50 mg vzorky karbetopendecínium bromidu do 50 ml odmernej banky, rozpustilo sa v 15 ml rozpúšťacieho roztoku (metanol + voda (1:10, v/v)) a doplnilo v odmernej banke po značku rozpúšťacím roztokom. Pre analýzu sa použila kolóna C18 (250x4,Omm, 5pm), mobilná fáza : 20% acetonitril, 80% roztok tetrabutylammonium dihydrogen fosfátu (c= 0,9 g/1), prietok : 1,2 ml/min., detekcia : UV 210 nm, dávkovaný objem : 20 μΐ, doba analýzy : 15 min., teplota 25°C. (Chromatogram na obr. 2) Obsah karbetopendecínium bromidu 98.5%.A 50 mg sample of carbetopendecin bromide was weighed into a 50 ml volumetric flask, dissolved in 15 ml of a solution solution (methanol + water (1:10, v / v)) and made up to the mark with a solvent solution in the volumetric flask. A C18 column (250x4, Omm, 5pm) was used for the analysis, mobile phase: 20% acetonitrile, 80% tetrabutylammonium dihydrogen phosphate solution (c = 0.9 g / l), flow rate: 1.2 ml / min, detection: UV 210 nm, dosing volume: 20 μΐ, analysis time: 15 min., Temperature 25 ° C. (Chromatogram in Fig. 2) Carbetopendecinium bromide content 98.5%.
Príklad 3Example 3
Stanovenie obsahu karbetopendecínium bromidu v očnej instilácii ml vzorky očnej instilácie s obsahom karbetopendecínium bromidu sa odpipetovalo do 10 ml odmernej banky a doplnilo po značku destilovanou vodou. Pre analýzu sa použila kolóna C18 (150x4,6mm, 5pm), mobilná fáza : 15% acetonitril, 85% roztok tetrabutylammonium dihydrogen fosfátu (c= lg/1), prietok : 1,0 ml/min., detekcia : UV 210 nm, dávkovaný objem : 20 μΐ, doba analýzy : 25 min., teplota 22°C. (Chromatogram na obr.3)Determination of carbetopendecin bromide content in the eye instillation ml of a sample of eye instillation containing carbetopendecin bromide was pipetted into a 10 ml volumetric flask and made up to the mark with distilled water. A C18 column (150x4.6mm, 5pm) was used for analysis, mobile phase: 15% acetonitrile, 85% tetrabutylammonium dihydrogen phosphate solution (c = 1g / l), flow rate: 1.0 ml / min, detection: UV 210 nm , dosing volume: 20 μΐ, analysis time: 25 min., temperature 22 ° C. (Chromatogram in Fig. 3)
Stanovilo sa 0.2mg karbetopendecínium bromidu na lml prípravku.0.2 mg of carbetopendecin bromide per ml formulation was determined.
s*with*
Príklad 4Example 4
Stanovenie obsahu karbetopendecínium bromidu v aerodisperzii ml vzorky aerodisperzie s obsahom účinnej zložky karbetopendecínium bromid sa odpipetovalo do 50 ml odmernej banky a doplnilo po značku destilovanou vodou. Pre analýzu sa použila kolóna C8 (250x4,6mm, 5pm), mobilná fáza : 20% acetonitril, 80% roztok tetraoktylammonium bromid (c= lg/1), prietok : 0,8 ml/min., detekcia : UV 210 nm, dávkovaný objem : 50 μΐ,. doba analýzy : 25 min., teplota 22°C. (Chromatogram na obr. 4)Determination of carbetopendecin bromide content in aerodispersion ml of an aerodispersion sample containing the active ingredient carbetopendecin bromide was pipetted into a 50 ml volumetric flask and made up to the mark with distilled water. C8 column (250x4.6mm, 5pm), mobile phase: 20% acetonitrile, 80% tetraoctylammonium bromide solution (c = 1g / l), flow rate: 0.8 ml / min, detection: UV 210 nm, dosing volume: 50 μΐ ,. analysis time: 25 min., temperature 22 ° C. (Chromatogram in Fig. 4)
Príklad 5Example 5
Stanovenie obsahu karbetopendecínium bromidu v aerodisperziiDetermination of carbetopendecinium bromide content in aerodispersion
Postupom analogicky ako v príklade 4, s tým že sa použije kolóna NH2 typu. Stanovilo sa 8mg karbetopendecínium bromidu na lml prípravku.By a procedure analogous to Example 4, using an NH2 type column. 8mg of carbetopendecin bromide per ml formulation was determined.
Claims (7)
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| Application Number | Priority Date | Filing Date | Title |
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| SK56-2006U SK4560U (en) | 2006-03-22 | 2006-03-22 | Intermediate link connecting the hydrospring to the running gear of a railway vehicle |
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| Publication Number | Publication Date |
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| SK562006A3 true SK562006A3 (en) | 2007-11-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK56-2006U SK4560U (en) | 2006-03-22 | 2006-03-22 | Intermediate link connecting the hydrospring to the running gear of a railway vehicle |
| SK56-2006A SK562006A3 (en) | 2006-03-22 | 2006-03-22 | A method for determining the content of carbetopendecin bromide by liquid chromatography |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK56-2006U SK4560U (en) | 2006-03-22 | 2006-03-22 | Intermediate link connecting the hydrospring to the running gear of a railway vehicle |
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| Country | Link |
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| EP (1) | EP2054286A2 (en) |
| SK (2) | SK4560U (en) |
| WO (1) | WO2007108782A2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE102008042198B4 (en) | 2008-09-18 | 2012-03-08 | Andreas Fiedler | Freight car bogie |
| EP2748047A1 (en) * | 2011-08-26 | 2014-07-02 | Aktiebolaget SKF | Railway bogie assembly, with two-part adapter assembly for hydraulic suspension |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2658471B1 (en) * | 1990-02-21 | 1992-06-12 | Sambre & Meuse Usines | LOAD WEIGHING BOGIE FOR RAILWAY VEHICLES. |
| ATE383292T1 (en) * | 2004-03-26 | 2008-01-15 | Skf Ab | BOGIE OF A RAILWAY VEHICLE |
| DE102005004721B4 (en) * | 2005-01-10 | 2009-09-24 | Ab Skf | Connection to a bogie of a rail vehicle |
-
2006
- 2006-03-22 SK SK56-2006U patent/SK4560U/en unknown
- 2006-03-22 SK SK56-2006A patent/SK562006A3/en unknown
-
2007
- 2007-02-16 WO PCT/SK2007/050006 patent/WO2007108782A2/en not_active Ceased
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| EP2054286A2 (en) | 2009-05-06 |
| SK4560U (en) | 2006-09-07 |
| WO2007108782A3 (en) | 2008-03-13 |
| WO2007108782A8 (en) | 2007-12-27 |
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