DEVELOPMENT OF METHODS FOR IDENTIFICATION OF

Огляди літератури, оригінальні дослідження, погляд на проблему

UDC 615.2-07]-092.4

DEVELOPMENT OF METHODS FOR IDENTIFICATION OF DESLORATADINE IN MEDICINES ©Liliya Logoyda SHEI «Ternopil state medical university named a fter I. Ya. Horbachevsky o f MPH o f Ukraine» SUMMARY. M ethods of ident if icat ion of des loratad ine in med ic ines by absorpt ion spectrophotom etry and TLC have been developed. KEY WORDS: desloratad ine, ident if icat ion, spectrophotom etery, th in layer chrom atography, val idat ion.

In tro d u c tio n . The cu rre n t pharm aceuti cal analys is has got more emphas is to sati sfy o ur query for better understanding of p hys icochemi cal propert ies of p harmaceuti cal compounds, by the use of advanced instrumental methods. It also plays an important part for qual ity assurance o f pharmaceuti cal product throughout the shelf life. The pharmaceuti cal industry is under increased scrut iny to constra in costs and yet consistently del iver to market safe, efficac ious products that fulfi ll med ical needs. As a part of t his, drug analys is also plays an important role. Standard analyti cal procedure for newer drugs or formati on may not be ava ilable in Pharmacopoe ia; it is essenti al to develop new analyti cal methods wh ich are accurate, prec ise, specific, linear, s imple and rap id. Desloratadi ne (8-chloro-6,11-d ihydro-11 -(4-p iperdinyl idene)-5Hbenzo[5,6]cyclohepta[1,2-b]pyri dine) is a med ic ine used to treat allergies. It is marketed under several trade names such as NeoClarityn, Claramax, Clari nex, Edem, Lar inex, Aeri us, Dazit, Azomyr, Deselex and Delot. It is an active metabol ite of loratadine (second generati on), wh ich is also on the pharmaceuti cal market. Desloratadine is a tricycl ic anti histam ine (t hird generation), wh ich has a selective and peri pheral H1-antagon ist act ion. It is an antagon ist at histam ine H1receptors, and an antagon ist at all subtypes of the muscari n ic acetylchol ine receptors. Desloratadine is a non-sedating, long-acting histam ine antagonist with selective peri pheral H1-receptor antagon ist activity. After oral adm inistrati on, desloratadi ne selectively blocks peripheral histam ine H1-receptors, because the substance is excluded from e ntry to the central nervous system. It has a long-lasting effect and in moderate and low doses, does not cause drows iness because it does not read ily enter the central nervous system. Unl ike other anti histam ines, desloratadine is also effective in rel ieving nasal congestion, parti cularly in pati ents with allerg ic rh initi s. Analys is of d es loratad ine is not descr ibed in Pharmacope ia, that’s why develop­ ment and val idati on of methods for determ inati on of desloratadine in med ic ines was our ma in aim [1]. We proposed and developed a method for spectrophotometri c and chromatograph ic identifi cati on of d es lora­ tadine in med ic ines. The aim of our study was to develop methods to identify desloratadine in med ic ines by methods

absorpti on spectrophotometry and th in layer chro­ matography. Materials and methods of research. The objects of the study were tablets tablets «Aeri us», tablets «Deslor», tablets «Aeriallerg», Pharmacopoe ial stan­ dard sample SPU desloratadine (certificate number 11/1-3187 of 08/13/14), purchased by the State Enterpri se «Ukra i n ian Research Pharmacopoei al Center Qual ity of drugs.” Analytical equipment: UV spectrophotom eter Lambda 25, Scales AVT-120-5D, measuri ng vessel glass and reagents that meet the SPU requ irements. TLC test was carri ed out us ing Silica gel, chromato­ graph ic plates 60 F254 «Merck» (Germany) and «Sorbf l» (Russ a). In develop ing the techn ique of identifi cati on data as part of de s loratadine med ic ines was chosen by UVspectrophotometry and TLC. Results and discussion. We had previously stud ied the behavi or of d esloratadine in the UV spectra us ing in different solvents (ethanol, water R, 0.1 mol/l soluti on of hydrochlori c ac i d). The behavior of desloratadine in the UV spectrum in different solvents showed that all drugs have character ist ic absorpti on bands i n the wavelength range (2 2 0 -3 6 0 nm). Absorpti on maxi mum of desloratadine: in ethanol when 244±2 nm; 0.1 M soluti on of hydrochlori c ac id at 280±2 nm; in water - at 244±2 nm and 273±2 nm (fig. 1). It makes it poss ible for the use of UV-spectrophotometry for analys is of desloratadi ne in med ic i nes [2]. We had i nvestigated various mob i le phases (solvent system) in order to identify the o pti mal cho ice of desloratadine investi gat ion by TLC in med ic ines. The factors of mob ility in the stud ied systems of deslora­ tadine solvents, are listed in table 1, 2. In order to develop methods of identifi cati on of desloratadine in d ifferent solvent system, we investi gated the sens itivity of detecti on desloratadine. The value detection lim it desloratadine and selection of opti mal developers us ing different mob ile phases are g iven i n table 1-2. We found that desloratadi ne identifi cati on by TLC us ing a sens itive of all investi gated solvents. Therefore, to identify a part deslorata­ dine tablets can be used TLC method. Establ ished that the most opti mal Rf observed us ing rmob ile phases:

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Огляди літератури, оригінальні дослідження, погляд на проблему

dіoxane-benzene-ammon іа (25 %) (7: 12: 1) and n-butanol-acet іc ac іd-water (1: 1: 1). The detect ion limit desloratad іпє іп these systems іs 0.2-0.4 mg.

However, the express solvent system n-butanol-aceti c ac іd-water (1: 1: 1) yi elds a solvent system d ioxanebenzene-ammon іa (25 %) (7: 12: 1).

Figure 1. Electron ic a bsorpt ion spectra for: 1 - solut ion from tablets «De s lor« (in 0.1 m ol/l solut ion of hydrochlori c ac id), 2 solut ion from tablets «Deslor« (in ethanol), 3 - solut ion from tablets «Deslor« (in w ater R), 4 - solut ion Pharmacopoe ial standard sample S PU of d e s loratad ine (in et hanol).

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Огляди літератури, оригінальні дослідження, погляд на проблему

Table 1. Chromatograph іс characteri st іcs ot d es loratad ine in d ifferent solvent systems M obile phase chloroform -acetone (8 : 2) n-butanol-m ethanol (3 : 2) chloroform -m ethanol (9 : 1) m ethanol-am m onia (25 % ) (100 : 1.5) dioxane-benzene-am m onia (25 %) (7 : 12 : 1) toluene-acetone-ethanol,-am m onia (25 %) (45 : 45: 7.5 : 2.5) ethylacetate-m ethanol-am m onia (25 % ) (85 : 10 : 5) n-butanol-acetic acid-w ater (1 : 1 : 1) ethanol-acetic acid-w ater (5 : 3 : 2)

The lim it o f detection, m icrogram s 0.4 0.2 0.4 0.4 0.4 0.4 0.6 0.2 0.4

Stationary phase (plate) R f o n «M erch» 0.05 0.18 0.24 0.28 0.42 0.20 0.13 0.48 0.36

Table 2. Chromatograph ic characterist ics of d e s loratadi ne in different solvent systems w ith different developers

D ioxanebenzeneam m onia (25 %) (7 : 12 : 1)

1

0,48

0,42

yellow

-

Thus, identificati on of d esloratadine med ic ines we offer TLC-method us ing solvent system d ioxanebenzene-ammon ia (25 %) (7 : 12 : 1) and stati onary phase - plate «Merch». The analys is cons idered probable, though the test requ irements «Check suitabi lity chromatograph ic system». Checking the suitability o f the chromatographic system. Chromatograph ic system is considered appropr ate when: - The chromatogram obta ined with reference solut ion is a clearly v is ible spot; - Rf pri nc ipal spot in the chromatogram o bta ined with reference solution to be about 0.6. Investigation solutions from tablets «Aerius», tablets «Deslor», tablets «Aeriallerg». To sample powder tablets or powder, equ ivalent to 0.01 g desloratadine, add 5.0 ml of ethanol R and d ilute with ethanol R to 10.0 ml, m ix and fi lter. Reference solution. 0.01 g Pharmacopoeialstandard sample SPU of desloratadine dissolved in ethanolR and d ilute with the same solvent to 10.0 ml. Mob ile phase: di oxane-benzene-ammonia (25 %) (7 : 12 : 1). Samples that are applied: 50 mg, appl ied the test soluti on and investi gati on solut ions. Over a path o f 10 cm from the starting line. Developer: Dragendorff reagent. Results: the chromatogram o bta ined with the test soluti on is detected at the ma in spot spots bas ic

b rom thym ol blue

n-butanolacetic acidw ater (1 : 1 : 1)

D rag en do rff reagent

D evelopers ( c o l o r z o n e ) sol. ninhydrine, t °

desloratadine

Rf M o b ile p h a s e V iew in ultraviolet light

Substance

light orange

orange

bluegreen

oGO