Usporedba HPLC metoda za analizu onečišćenja azitromicinskih proizvoda

professional thesis

• Author: Marin Blagović
• Mentor: Biljana Nigović (mentor)
• Committee member: Biljana Nigović (predsjednik povjerenstva)
• Committee member: Ana Mornar Turk (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2019-04-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

CILJ RADA
Azitromicin je makrolidni antibiotik koji se koristi za liječenje bakterijskih infekcija.
Danas se nalazi na tržištu u obliku tableta, sirupa, kapsula i injekcija. Jedno od
analitičkih ispitivanja koja se provode u kontroli kvalitete gotovih proizvoda azitromicina
je analiza onečišćenja (srodnih spojeva i razgradnih produkata). Cilj ovog rada je
opisati i objasniti kromatografske metode za analizu onečišćenja u proizvodima
azitromicina koje se koriste u kontroli njihove kvalitete. Prikazane su sličnosti i razlike
navedenih metoda te su uspoređene s farmakopejskim metodama za analizu
onečišćenja azitromicina.
MATERIJALI I METODE
Onečišćenja mogu nastati tijekom proizvodnje ili skladištenja farmaceutskog proizvoda
i njihov sadržaj se mora kontrolirati. Onečišćenja azitromicina se analiziraju tehnikom
tekućinske kromatografije visoke djelotvornosti (HPLC) u svim vrstama dozirnih oblika.
U analitici azitromicinskih proizvoda UV detektori se koriste za detekciju onečišćenja u
tabletama, kapsulama i injekcijama azitromicina, dok se elektrokemijski detektor (EC)
koristi za detekciju onečišćenja u sirupima azitromicina. Opisani su eksperimentalni
uvjeti HPLC metoda: vrste stacionarnih faza, vrste i brzine protoka mobilnih faza,
gradijente eluacije, načini detekcije, pripreme otopina standarda i ispitivanje
prikladnosti sustava. U tablicama su prikazani kromatografski parametri za
identifikaciju pikova onečišćenja u azitromicinskim proizvodima.
RASPRAVA
Metode za analizu onečišćenja u tabletama, kapsulama i injekcijama azitromicina
koriste istu kolonu, iste instrumentalne uvjete, iste kalibracijske i identifikacijske
otopine Postoji razlika u zahtjevima za provjeru prikladnosti sustava i na nju treba
obratiti pažnju ukoliko se paralelno na istom instrumentu analiziraju uzorci tableta,
kapsula ili injekcija. Ukoliko se provjere svi uvjeti za ispitivanje prikladnosti sustava
nema prepreke za analizu ovih vrsta uzoraka paralelno na istom sustavu. Slično se
može zaključiti za uzorke sirupa azitromicina. Sve doze i formulacije sirupa se mogu
analizirati paralelno na istom sustavu s elektrokemijskim detektorom ukoliko se obrati
pažnja na ispunjavanje svih uvjeta prikladnosti sustava.
ZAKLJUČAK
U redovnoj analitici farmaceutskih proizvoda u laboratorijima kontrole kvalitete od
velike je važnosti da se analize različitih doza ili formulacija s istom djelatnom tvari
mogu raditi zajedno na istom kromatografskom sustavu. Ukoliko usporedimo metodu
za analizu onečišćenja u azitromicin injekcijama koja se koristi u Plivi s onom u
farmakopeji, vidljivo je da je farmakopejska metoda složenija i da bi samo za analizu
onečišćenja injekcija vjerojatno trebalo više radnih dana i više analitičara. Tako bi se
smanjila produktivnost laboratorija i broj analiza koje se izvrše u jedinici vremena, što
u konačnici može dovesti do skupljeg lijeka za pacijenta.

Abstract (english)

AIM OF WORK
Azithromycin is a macrolide antibiotic used to treat bacterial infections. Today, it is
marketed in the form of tablets, syrups, capsules and injections. One of the analytical
tests carried out in the quality control of finished products of azithromycin is the
analysis of impurities (related compounds and degradation products). The aim of this
paper is to describe and explain chromatographic methods for analysis of impurities in
azithromycin products which are used in their quality control. The similarities and
differences of the methods are shown and compared with the pharmacopoeial
methods for the analysis of azithromycin degradation products.
MATERIALS AND METHODS
Amount of degradation products may arise during the manufacture or storage of a
pharmaceutical product and their content must be controlled. Azithromycin degradation
products are analyzed by High Performance Liquid Chromatography (HPLC) in all
types of dosage forms. In the analysis of azithromycin finished products UV detectors
are used for detecting impurities in tablets, capsules and azithromycin injections, while
the electrochemical detector (EC) is used to detect impurities in azithromycin syrups.
The experimental conditions of the HPLC methods are described: stationary phase
types, types and rates of mobile phase flow, gradient elution, detection methods,
standard solution preparation and system suitability test. The tables show the
chromatographic parameters used for the identification of degradation product peaks
in azithromycin products.
DISCUSSION
Methods for analysis of degradation products in tablets, capsules and azithromycin
injections use the same column, the same instrumental conditions, the same
calibration and identification solutions. There is a difference in system suitability check
requirements and attention should be paid if the samples of tablets, capsules or
injections are analyzed together. If all the conditions for the system suitability test are
checked, there are no obstacles to the analysis of these types of samples in parallel in
the same system. Similar can be concluded for samples of azithromycin syrups. All
dosages and formulations of the syrups can be analyzed together on the same system
with an electrochemical detector if attention is paid to the fulfillment of all system
suitability conditions.
CONCLUSION
In a regular analytics of pharmaceutical products in quality control labs it is of great
importance that analyzes of different doses or formulations with the same active
substance can be performed together on the same chromatographic system. If we
compare the method for the analysis of azithromycin injections used in Pliva with those
in Pharmacopoeia, it is apparent that the pharmacopoeia method is more complex and
that it would probably take more days and more analysts to analyze degradation
products in samples of azithromycin injections. This would reduce the laboratory's
productivity and the number of analyzes performed in the unit of time, which ultimately
can lead to a more expensive drug for the patient.

• Keywords: azitromicin; analiza onečišćenja; kontrola kvalitete; tekućinska kromatografija visoke djelotvornosti; HPLC
• Keywords (english): azithromycin; analysis of impurities; quality control; high performance liquid chromatography; HPLC
• Language: croatian
• URN:NBN: urn:nbn:hr:163:983634
• Study programme: Title: Drug development; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni magistar/sveučilišna magistra razvoja lijekova (sveučilišni magistar/sveučilišna magistra razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-12-18 14:43:35