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Heavy metals in formulated dietary supplements for the treatment of inflammatory bowel diseases
Upalne bolesti crijeva su teške bolesti s nuspojavama koje utječu na svakodnevni život pacijenata koji od njih boluju. Mnogi uz standardnu farmakoterapiju uzimaju i razne dodatke prehrani. Među njima su i biljni pripravci kurkume, justicije i indijskog tamjanovca koji se koriste za ublažavanje simptoma upalnih bolesti crijeva. Osim bioaktivnih molekula koje se prirodno nalaze u ovim biljkama i koje pokazuju farmakološki učinak, mogu se naći i razna onečišćenja kao naprimjer teški metali.. Teški metali nemaju fiziološku funkciju u ljudskom tijelu i osim toga imaju potencijal biti iznimno toksični. U ovom radu se određivao sadržaj olova, arsena i cinka u 12 dodatak prehrani s ciljem procjene sigurnosti njihove primjene.. Koncentracija metala je određena atomskom apsorpcijskom spektrometrijom grafitnom tehnikom nakon prvotne mikrovalne digestije uzoraka. Izračunata je količina teških metala koja bi se unijela u jednoj dozi i dnevno prateći upute proizvođača i od 12 uzoraka jedan od njih prelazi dozvoljeni dnevni unos za olovo prema ICH smjernicama. U pripravcima su dokazane varijabilne koncentracije teških metala što ukazuje na potrebu temeljite kontrole sigurnosti ovakvih dodataka prehrani.Inflammatory bowel diseases are crippling diseases that have a severe impact on the everyday life of its patients. Many such patients take various dietary supplements in addition to their standard pharmacotherapy. Among them exist herbal supplements based on turmeric, green chiretta and Indian frankincense which are used to alleviate the symptoms of inflammatory bowel diseases. In addition to the bioactive molecules that are naturally found in these plants and that show a pharmacological effect, various pollutants can be found, such as heavy metals. Heavy metals have no physiological function in the human body and, in addition, have the potential to be extremely toxic. In this study, the content of lead, arsenic and zinc in 12 dietary supplements was determined with the aim of assessing the safety of their use. Metal concentration was determined by atomic absorption spectrometry using the graphite technique after initial microwave digestion of the samples. The amount of heavy metals that would be ingested in a singular and daily dose following the recommended intake by the manufacturer was calculated, and out of 12 samples, one of them exceeded the permitted daily intake for lead according to ICH guidelines. Variable concentrations of heavy metals have been proven in the preparations, which indicates the need for thorough control of the safety of such dietary supplements
The distribution of botulinum toxin type A in the rat brain after peripheral application
Iako predstavlja najpotentniji otrov poznat čovječanstvu, botulinum toksin tipa A (BT-A) tijekom posljednjih 30-ak godina pronašao je svoje mjesto u terapiji različitih stanja praćenih mišićom hiperkontraktilnošću. Novija ispitivanja ukazala su na njegov antinociceptivni učinak, pri čemu kronična migrena predstavlja prvu bolnu indikaciju za koju je odobren. Osim migrene, pokazuje veliki potencijal i u terapiji različitih vrsta neuropatske boli. Uz terapijsku primjenu, postao je i neizostavni dio u suvremenoj estetskoj medicini, te jedan od globalno najpopularnijih estetskih zahvata, pri čemu je smatran kao siguran i bez ozbiljnih štetnih nuspojava. Dokazi o među-sinaptičkom transportu BT-A u vizualnom, motornom i senzornom sustavu dodatno su potvrdili hipotezu o središnjem mehanizmu djelovanja na bol, s obzirom da BT-A retroaksonalnim transportom s periferije dolazi do prve sinapse unutar leđne moždine, gdje interferira s različitim neurotransmiterskim sustavima. Stoga, postavlja se pitanje ostaje li BT-A na razini leđne moždine ili se transinaptičkim prijenosom prenosi dalje u supraspinalne regije. Cilj ovog istraživanja bilo je ispitati distribuciju BT-A unutar hipotalamusa, hipokampusa, gracilne te facijalne jezgre, nakon jednostrane periferne primjene u stražnju šapu štakora. Imunohistokemijskom metodom praćen je indirektni pokazatelj proteolitičke aktivnosti BT-A, pokidani fragment SNAP-25 proteina. Signal pokidanog SNAP-25 detektiran je unutar svih promatranih regija, pri čemu je kod skupine kojoj je primijenjen specifičan antitoksin za BT-A, uočeno smanjenje intenziteta signala. Taj učinak rezultat je neutralizacije dijela izvanstaničnog BT-A antitoksinom te indirektni dokaz među-sinaptičkog prijenosa BT-A u središnjem živčanom sustavu. Prikazani rezultati otvaraju brojna pitanja o značenju ovih nalaza, posebice u kontekstu sigurnosti dugotrajne primjene BT-A, te zahtijevaju daljnja ispitivanja.Although it represents the most potent toxin known to humanity, botulinum toxin type A (BT-A) has found its place over the last 30 years in the therapy of various conditions accompanied by muscle hypercontractility. Recent studies have indicated its antinociceptive effect, with the first case of approval as treatment for chronic migraine. Besides migraine, it shows great potential in the therapy of various types of neuropathic pain. In addition to therapeutic use, it has also become an indispensable part of modern aesthetic medicine and one of the most popular aesthetic procedures, generally being accepted as safe and without serious adverse side effects. Evidence of BT-A's trans-synaptic transport in the visual, motor, and sensory systems has further confirmed the hypothesis of a central mechanism of action on pain, given that BT-A reaches the first synapse within the spinal cord through retroaxonal transport from the periphery, where it interferes with various neurotransmitter systems. Therefore, the question arises whether BT-A remains at the spinal cord level or is transported trans-synaptically to supraspinal regions. The aim of this research was to examine the distribution of BT-A within the hypothalamus, hippocampus, gracile, and facial nuclei after unilateral peripheral administration to the hind paw of rats. The immunohistochemical method tracked an indirect indicator of BT-A proteolytic activity, the cleaved fragment of the SNAP-25 protein. The signal of cleaved SNAP-25 was detected within all observed regions, with a reduction in signal intensity noted in the group treated with a specific antitoxin for BT-A. This effect is the result of the neutralization of a part of extracellular BT-A by the antitoxin and an indirect proof of BT-A trans-synaptic transport in the central nervous system. The presented results raise numerous questions about the significance of these findings, especially in the context of the safety of long-term BT-A use, and require further investigation
Validation of the MEKC-MS/MS method for quantitative analysis of anastrozole and letrozole in human plasma
Inhibitori aromataze anastrozol i letrozol koriste se u liječenju o estrogenu ovisnog i HER2
negativnog raka dojke kod postmenopauzalnih pacijentica, kao monoterapija ili u kombinaciji s
drugim lijekovima poput CDK4/6 inhibitora. Praćenje pridržavanja pacijentica ovako dugotrajnoj
terapiji ključno je za postizanje željenih ishoda liječenja.
Glavni cilj ovog diplomskog rada bio je validirati brzu i jednostavnu novorazvijenu MEKC-MS/MS
metodu za analizu inhibitora aromataze anastrozola i letrozola u biološkim uzorcima, što je važno
za terapijsko praćenje lijekova. Ispitivani validacijski parametri bili su linearnost i kalibracijska
krivulja, točnost i preciznost, stabilnost uzoraka u autosampleru te utjecaj matrice.
Validacija metode pokazala je da matrica ne predstavlja analitički problem prilikom ispitivanja
anastrozola (ME<1,3%) i letrozola (ME<17,3%). Parametar linearnosti ove analitičke metode
zadovoljen je za anastrozol (r>0,9945) u zadanom koncentracijskom rasponu od 20 do 200 ng/mL
kao i za letrozol (r>0,9802) u zadanom koncentracijskom rasponu od 30 do 300 ng/mL. Točnost i
preciznost (odstupanje, RSD<15%, odnosno <20% za LLOQ) zadovoljavajuće su za oba analita.
Također, stabilnost anastrozola i letrozola u autosampleru potvrđena je (odstupanje, RSD<15%), što
doprinosi pouzdanosti same metode.Aromatase inhibitors anastrozole and letrozole are used in the treatment of estrogen-dependent and
HER2-negative breast cancer in postmenopausal patients, either as monotherapy or in combination
with other drugs such as CDK4/6 inhibitors. Monitoring patient adherence to such long-term therapy
is crucial for achieving desired treatment outcomes.
The main objective of this thesis was to validate a fast and simple newly developed MEKC-MS/MS
method for the analysis of aromatase inhibitors anastrozole and letrozole in biological samples,
which is important for therapeutic drug monitoring. The validation parameters tested included
linearity and calibration curve, accuracy and precision, sample stability in the autosampler, and
matrix effect.
The method validation demonstrated that the matrix does not pose an analytical problem for the
analysis of anastrozole (ME<1.3%) and letrozole (ME<17.3%). The linearity parameter of this
analytical method was met for anastrozole (r>0.9945) in the specified concentration range of 20 to
200 ng/mL, as well as for letrozole (r>0.9802) in the specified concentration range of 30 to 300
ng/mL. Accuracy and precision (bias, RSD<15%, and <20% for LLOQ) were satisfactory for both
analytes. Additionally, the stability of anastrozole and letrozole in the autosampler was confirmed
(bias, RSD<15%), contributing to the reliability of the method itself
Dietary intake of minerals among the student population
U okviru ovog istraživanja procijenjen je nutritivni unos mineralnih elemenata (natrija, kalija, cinka, magnezija, željeza, fosfora, bakra, kalcija) među studentima 3. godine Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu te su dobivene vrijednosti uspoređene s preporučenim unosom. Ispitivanjem je obuhvaćeno ukupno 382 ispitanika (98 muških i 284 ženskih) prosječne dobi 21,5 godina tijekom tri akademske godine 2020./2021., 2021./2022. i 2022./2023. Unos mikronutrijenata procijenjen je na temelju četverodnevnih dnevnika prehrane pri čemu su prikupljeni podaci analizirani uz pomoć računalnog programa Prehrana i statistički obrađeni. Rezultati su pokazali da su medijani dnevnog unosa natrija, fosfora i bakra za oba spola veći od preporučenog dok su medijani dnevnog unosa kalija, kalcija, magnezija i cinka manji od preporučenih vrijednosti za oba spola. Unos željeza je bio zadovoljavajući kod studenata, dok je nedostatan unos željeza zabilježen kod studentica. Studenti farmacije su unosili manje kalija, kalcija, magnezija, fosfora, željeza i cinka u usporedbi s podacima iz dostupne literature, dok je unos bakra bio veći. Unos natrija studenata približno je odgovarao podacima istraživanja drugih autora. Nezadovoljavajući rezultati ukazuju da je nužna dodatna edukacija studenata kako bi uveli promjene u vlastitoj prehrani s ciljem prevencije zdravstvenih problema u kasnijoj životnoj dobi. Također, kao zdravstveni radnici biti će dužni savjetovati pacijente o važnosti pravilne prehrane u svrhu održavanja zdravlja i pomoći kod bolesti.In this study, the dietary intake of minerals (sodium, potassium, zinc, magnesium, iron, phosphorus, copper, calcium) was assessed among 3rd-year students of the Faculty of Pharmacy and Biochemistry, University of Zagreb, and results were compared with the recommended values. The survey included a total of 382 students (98 male and 284 female) with an average age of 21.5 years in the three academic years 2020/2021, 2021/2022 and 2022/2023. The students kept a food diary for four days, and the collected diaries were analyzed using the Prehrana program. The obtained results were statistically analyzed. The results showed that median daily intake of sodium, phosphorus and copper was above the recommended values in both sexes, while the median daily intake of potassium, calcium, magnesium and zinc was below the recommended values, also in both sexes. Iron intake was adequate in male students, while female students were found to have inadequate iron intake. Pharmacy students consumed less potassium, calcium, magnesium, phosphorus, iron and zinc compared to data from the available literature, while copper intake was higher. The students sodium intake was similar to research data from other authors. The results indicate that additional education of students about proper nutrition is necessary in order to avoid health problems later in life. Furthermore, as healthcare professionals, they will be required to counsel their patients on the importance of healthy lifestyle with the purpose of maintaining health and helping with illness
Optimization of fragmentation conditions for alpelisib and deuterated abemaciclib in a triple quadrupole mass spectrometer
Rak dojke je najčešća zloćudna novotvorina u žena, a njegova prevalencija širom svijeta raste.
Personalizirani pristup je bitan dio liječenja, stoga je važno razviti specifične analitičke metode za
istraživanje lijekova. Alpelisib i abemaciklib su se pokazali učinkovitim lijekovima u liječenju hormonski
ovisnog raka dojke. Oba djeluju na signalne puteve koji su važni za stanični rast i proliferaciju te
posljedično, rast tumora. Cilj ovog istraživanja je bio optimizirati uvjete fragmentacije alpelisiba i
deuteriranog abemacikliba u trostrukim kvadrupolima dva različita spektrometra masa, Agilent Ultivo i
Agilent 6470. Određene su optimalne vrijednosti fragmentorskih napona i kolizijskih energija, te je
provedena identifikacija i kvantifikacija ključnih fragmenata specifičnih za ove spojeve. U Agilent Ultivo
spektrometru masa uz pozitivnu ionizaciju elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti
442,1 uz fragmetorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 328,0, 114,7, 288,0 i 273,1
uz kolizijske energije od 25, 15 45 i 60 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti
515,2 uz fragmentorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 176,8, 393,0 i 351,3 uz
kolizijske energije od 105, 25 i 70 eV. U Agilent 6470 spektrometru masa uz pozitivnu ionizaciju
elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti 442,2, uz fragmentorski napon od 140 V.
Nastaju fragmentni ioni m/z vrijednosti 328,1 115,0, 288,1, 273,0 i 129,0 uz kolizijske energije od 25, 15,
50, 60 i 105 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti 515,3 uz fragmentorski napon
od 120 eV. Nastaju fragmentni ioni od 177,0, 393,1 i 244,9 uz kolizijske energije od 105, 25 i 75 eV.
Provedena je analiza i uz negativnu ionizaciju elektroraspršenjem, gdje se ova metoda pokazala manje
osjetljivom.Breast cancer is the most common malignant tumor in women, and its prevalence is increasing worldwide.
A personalized approach is a crucial part of treatment, making it important to develop specific analytical
methods for drug research. Alpelisib and abemaciclib have proven to be effective drugs in the treatment of
hormone-dependent breast cancer. Both act on signaling pathways important for cell growth and
proliferation, and consequently, tumor growth.The aim of this study was to optimize the fragmentation
conditions for alpelisib and deuterated abemaciclib in triple quadrupoles of two different mass
spectrometers, the Agilent Ultivo and Agilent 6470. Optimal values for fragmentor voltages and collision
energies were determined, and identification and quantification of key fragments specific to these
compounds were conducted.In the Agilent Ultivo mass spectrometer with positive electrospray ionization,
alpelisib produces a molecular ion with an m/z value of 442,1 at a fragmentor voltage of 120 V. Fragment
ions with m/z values of 328,0, 114,7, 288,0, and 273,1 are formed with collision energies of 25, 15, 45, and
60 eV, respectively. Deuterated abemaciclib produces a molecular ion with an m/z value of 515.2 at a
fragmentor voltage of 120 V. Fragment ions with m/z values of 176,8, 393,0, and 351,3 are formed with
collision energies of 105, 25, and 70 eV, respectively.In the Agilent 6470 mass spectrometer with positive
electrospray ionization, alpelisib produces a molecular ion with an m/z value of 442,2 at a fragmentor
voltage of 140 V. Fragment ions with m/z values of 328,1, 115,0, 288,1, 273,0 and 129,0 are formed with
collision energies of 25, 15, 50, and 105 eV, respectively. Deuterated abemaciclib produces a molecular ion
with an m/z value of 515,3 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 177,0,
393,1, and 244,9 are formed with collision energies of 105, 25, and 75 eV, respectively. Analysis was also
conducted using negative electrospray ionization, where this method proved to be less sensitive
Determination of the physical and chemical properties of Laurel hydrolates from the Ariatic coast
Lovor (Laurus nobilis L.) je sredozemna biljka koja se zbog ljekovitosti i aromatičnih svojstava
koristi u prehrambenoj, farmaceutskoj i kozmetičkoj industriji. Hidrolat lovora, iako u manjoj
koncentraciji od eteričnog ulja, sadrži ljekovite sastavnice antioksidativnog, protuupalnog i
antibakterijskog djelovanja. U ovome je radu ispitana kvaliteta i čistoća hidrolata listova lovora koji
su prikupljeni u različitim dijelovima Jadrana (Sjeverni, Srednji i Južni) kao i među hidrolatima
suhog i svježeg lista. Kvaliteta i čistoća hidrolata procijenjena je mjerenjem pH vrijednosti koja je
bila između 3,60 i 4,26, mutnoće koja je bila u rasponu od 0,72 do 3,41 NTU, indeksa refrakcije koji
je bio između 1,3331 i 1,3334 nd, relativne gustoće koja je bila u rasponu od 0,9590 do 1,0239,
kiselinskog broja koji je bio ispod 0,1 mg KOH/g te određivanjem sadržaja eteričnog ulja koji je bio
između 0,007 % i 0,014 %. Dobiveni su rezultati uspoređeni s vrijednostima fizikalno-kemijskih
parametara za hidrolate drugih aromatičnih biljaka iz literature budući da nema dostupnih
referentnih vrijednosti za hidrolat lovora. Provedena su ispitivanja pokazala da nema značajnih
razlika u kakvoći među uzorcima hidrolata. Zbog sve veće upotrebe hidrolata lovora u prehrambene,
medicinske i kozmetičke svrhe potrebno je uvesti standardizirane metode s referentnim
vrijednostima fizikalno-kemijskih parametara za utvrđivanje njihove ispravnosti.Bay Laurel (Laurus nobilis L.) is a Mediterranean plant widely used in the food, pharmaceutical and
cosmetic industries due to its medicinal and aromatic properties. Bay laurel hydrosol, although in a
lower concentration than in essential oil, contains bioactive constituents with antioxidant, antiinflammatory
and antibacterial activities. This study examined the quality and purity of bay laurel
hydrosols obtained from leaves collected from different regions of the Adriatic (Northern, Central
and Southern) as well as the differences between hydrosols made from dried and fresh leaves. The
quality and purity of the hydrosols were assessed by measuring pH (ranging from 3.60 to 4.26),
turbidity (0.72 to 3.41 NTU), refractive indeks (1.3331 to 1.3334), relative density (0.9590 to
1.0239), acid value (below 0,1 g KOH/g), and essential oil content (between 0,007% and 0,014%).
Since there are no reference values available for bay laurel hydrosol, the obtained results were
compared with the physical and chemical parameters of hydrosols from the other aromatic plants.
The analyses showed no significant differences in quality among the different hydrosol samples.
Given the growing use of laurel hydrosol in nutrition, medicine, and cosmetics, it is necessary to
introduce standardized methods and reference values for its physical and chemical parameters to
ensure its safe and effective use in humans
The impact of the cosmetics industry on today's beauty standards
Ljudsko lice ima značajan utjecaj na kvalitetu života, stavove i mentalno stanje pojedinca, te je njihov društveni život i
mentalno stanje izravno povezan s njihovim vanjskim izgledom. Nedavni naglasak na platformskoj komunikaciji i dijeljenju
slika povećao je interes za idealizirani fizički izgled, što je rezultiralo opsesivnom borbom za ljepotom. Privlačnost lica utječe
na samopouzdanje, odabir partnera te nudi prednosti u radnom i društvenom okruženju. Estetski ideali evoluirali su kroz
povijest, a mediji danas igraju ključnu ulogu u oblikovanju tih standarda. Društvo promiče kulturu mladosti, dok starenje
postaje sveprisutnije, što dovodi do nejednakosti između idealiziranih standarda i stvarnosti. Kozmetička industrija igra važnu
ulogu u definiranju i ispunjavanju standarda ljepote, ali istovremeno može pojačati stigmu povezanu s kožnim poremećajima,
što utječe na samopoštovanje i društvenu interakciju pojedinaca. Kozmetička industrija ima znatne mogućnosti u terapiji akni
vulgaris, pri čemu se ističu sastojci poput topikalnih retinoida, salicilne kiseline, niacinamida, α-hidroksi kiselina i benzoil
peroksida. Sastojci poput pčelinjeg otrova, probiotika, prebiotika i bakuchiola također pokazuju obećanje u borbi protiv akni.
Što se tiče rosacee, kozmetička industrija nema mnogo opcija za liječenje, ali su neki sastojci poput azelaične kiseline i Centella
asiatica pokazali određene koristi. Unatoč tome, fokus je na ublažavanju crvenila i smirivanju kože, iako to ne rješava samu
srž problema. Hiperpigmentacijski poremećaji su teški za rješavanje, a najbolje opcije tretmana uključuju N-acetil glukozamin,
niacinamid, retinoide i glikolnu kiselinu. UV izloženost igra ključnu ulogu u hiperpigmentaciji, pa je važno naglasiti važnost
korištenja proizvoda s faktorom zaštite od sunca. Kada je riječ o zreloj koži, kozmetička industrija ima širok raspon sastojaka
koji se koriste za ublažavanje znakova starenja, uključujući retinoide, vitamin C, peptide, nikotinamid, feruličnu kiselinu,
koenzim Q10, zeleni čaj, egzosome i antioksidanse. Iako kozmetička industrija pruža određene mogućnosti za rješavanje
različitih kožnih problema, postoje i ograničenja, posebno kada je riječ o složenijim stanjima poput rosacee i
hiperpigmentacije. Ipak, budućnost kozmetičke industrije obećava dinamičan razvoj usmjeren na ispunjavanje sve složenijih
standarda ljepote, uključujući personalizaciju proizvoda, upotrebu održivih praksi i transparentnost u vezi sa sastojcima.
Inovacije u znanstvenim istraživanjima dovest će do razvoja novih i učinkovitijih sastojaka za njegu kože, dok će digitalna
transformacija omogućiti potrošačima bolji pristup proizvodima i informacijama o njimaThe human face has a significant impact on quality of life, attitudes, and mental state of individuals, and their social life and
mental state are directly linked to their external appearance. The recent emphasis on platform communication and image
sharing has increased interest in an idealized physical appearance, resulting in an obsessive pursuit of beauty. Facial
attractiveness affects self-confidence, partner selection, and offers advantages in work and social environments. Aesthetic
ideals have evolved throughout history, and the media today plays a key role in shaping these standards. Society promotes a
culture of youthfulness, while aging becomes more prevalent, leading to a disparity between idealized standards and reality.
The cosmetic industry plays an important role in defining and fulfilling beauty standards, but at the same time, it can exacerbate
the stigma associated with skin disorders, affecting individuals' self-esteem and social interaction. The cosmetic industry has
significant potential in the therapy of acne vulgaris, with ingredients such as topical retinoids, salicylic acid, niacinamide, αhydroxy acids, and benzoyl peroxide being highlighted. Ingredients such as bee venom, probiotics, prebiotics, and bakuchiol
also show promise in the fight against acne. Regarding rosacea, the cosmetic industry does not have many treatment options,
but some ingredients such as azelaic acid and Centella asiatica have shown certain benefits. Nevertheless, the focus is on
reducing redness and calming the skin, although this does not address the root cause of the problem. Hyperpigmentation
disorders are difficult to treat, and the best treatment options include N-acetyl glucosamine, niacinamide, retinoids, and glycolic
acid. UV exposure plays a crucial role in hyperpigmentation, so it is important to emphasize the importance of using products
with sun protection factor. When it comes to mature skin, the cosmetic industry has a wide range of ingredients used to alleviate
signs of aging, including retinoids, vitamin C, peptides, niacinamide, ferulic acid, coenzyme Q10, green tea, exosomes, and
antioxidants. Although the cosmetic industry provides some opportunities to address various skin problems, there are
limitations, especially when it comes to more complex conditions such as rosacea and hyperpigmentation. However, the future
of the cosmetic industry promises dynamic development aimed at meeting increasingly complex beauty standards, including
product personalization, the use of sustainable practices, and transparency regarding ingredients. Innovations in scientific
research will lead to the development of new and more effective skincare ingredients, while digital transformation will enable
consumers to have better access to products and information about them
Attitudes of pharmacists in Croatia towards the independent pharmacist prescribing program
Posljednjih desetljeća farmaceutska struka prolazi kroz značajne promjene diljem svijeta, s naglaskom na proširenje uloga
ljekarnika izvan tradicionalnih okvira izdavanja lijekova. Jedan od smjerova takvih promjena je i koncept samostalnih
farmaceuta propisivača (eng. Independent pharmacist prescriber) koji je uspješno implementiran u nekoliko zemalja svijeta.
Samostalnim farmaceutima propisivačima u Velikoj Britaniji, u 2024. godini, dopušteno je procijeniti pacijente, postaviti
dijagnozu i propisati lijek za bilo koje stanje ili bolest (isključujući diamorfin, kokain i dipipanon), te za bilo kojeg pacijenta
unutar njihovih kliničkih kompetencija. Opseg djelovanja ovih farmaceuta širok je i obuhvaća rad na razini primarne i
sekundarne zdravstvene zaštite.
Cilj ovog istraživanja bio je utvrditi stavove hrvatskih ljekarnika prema programu samostalnih farmaceuta propisivača (eng.
Independent pharmacist prescriber). Putem on-line anketnog upitnika ispitanici su mogli izraziti svoje stavove prema
programu, njegovim prednostima i nedostatcima, ali i njegovoj potencijalnog implementaciji i izvođenju u Republici
Hrvatskoj.
U istraživanju je sudjelovalo 455 ispitanika, od kojih je 82,6% bilo žena, a 17,4% muškaraca, te je medijan dobi iznosio 34
godine. Većina ispitanika (85,5%) smatra da bi propisivanje lijekova od strane farmaceuta imalo pozitivan utjecaj na
zdravstveni sustav. Također, svaka navedena prednost ocijenjena je većinski kao iznimno važna. „Neprihvaćanje od strane
liječnika“ hrvatski su ljekarnici ocijenili kao najveću prepreku u okviru potencijalne implementacije programa, a „Vremenska
ograničenja“ kao najmanju. Gotovo su svi ispitanici smatrali kako uloga farmaceuta kao propisivača lijekova predstavlja
profesionalno napredovanje, a 63,5% ispitanika u potpunosti se složilo kako bi postali samostalni farmaceuti propisivači, kada
bi to bila mogućnost. Dodatna obuka nakon fakulteta, specijalistički studij i kurikulum fakulteta bili su najčešći odgovori na
pitanje gdje i na koji način bi se trebala odvijati obuka za stjecanje titule samostalnog farmaceuta propisivača.
Zaključno, stav hrvatskih ljekarnika prema programu samostalnih farmaceuta propisivača (eng. Independent pharmacist
prescriber) vrlo je pozitivan i optimističan, a približno dvije trećine ljekarnika izrazilo je želju za postizanjem titule
samostalnog farmaceuta propisivača. Ovi rezultati sugeriraju želju hrvatskih ljekarnika za daljnjim napredovanjem i
usavršavanjem, te upućuju na potrebu za raspravom o potencijalnim proširenjima uloga ljekarnika u sklopu hrvatskog
zdravstvenog sustava.In recent decades, the pharmaceutical profession has undergone significant changes worldwide, with a focus on
expanding the roles of pharmacists beyond the traditional framework of dispensing medications. One direction of these
changes is the concept of independent pharmacist prescribers, which has been successfully implemented in several
countries worldwide. In the UK, as of 2024, independent pharmacist prescribers are allowed to assess patients, diagnose,
and prescribe medications for any condition or illness (excluding diamorphine, cocaine, and dipipanone), as well as for
any patient within their clinical competence. The scope of these pharmacists' work is broad, covering both primary and
secondary healthcare.
The aim of this research was to determine the attitudes of Croatian pharmacists towards the independent pharmacist
prescriber program. Through an online survey, respondents were able to express their views on the program, its
advantages and disadvantages, as well as its potential implementation and execution in Croatia.
The study involved 455 respondents, 82.6% of whom were women, and 17.4% men, with a median age of 34. Most
respondents (85.5%) believe that pharmacist prescribing would have a positive impact on the healthcare system.
Additionally, all listed advantages were predominantly rated as extremely important. "Lack of acceptance by doctors"
was seen by Croatian pharmacists as the biggest obstacle to the potential implementation of the program, while "Time
constraints" were considered the smallest obstacle. Nearly all respondents believed that the role of pharmacists as
prescribers represents professional development, and 63.5% strongly agreed that they would become independent
pharmacist prescribers if given the opportunity. Postgraduate training, specialist studies, and university curriculum were
the most common answers regarding how and where the training for achieving the title of independent pharmacist
prescriber should take place.
In conclusion, the attitudes of Croatian pharmacists towards the independent pharmacist prescriber program are very
positive and optimistic, with approximately two-thirds expressing a desire to obtain the title. These results suggest a
strong willingness for further professional development and point to the need for discussions on potential expansions of
pharmacists' roles within the Croatian healthcare system
Optimization of fragmentation conditions for deuterated letrozole and deuterated ribociclib in a triple quadrupole mass spectrometer
Ribociklib je antineoplastik indiciran za liječenje postmenopauzalnih žena s lokalno uznapredovalim ili metastatskim
rakom dojke koji je HR pozitivan i HER2 negativan. Koristi se u kombinaciji s hormonskom terapijom koja smanjuje
učinak estrogena, a jedan od takvih lijekova je letrozol (inhibitor aromataze). Prilikom razvoja bioanalitičkih metoda
za terapijsko praćenje ovih lijekova ključna je uporaba unutarnjih standarda, koji eliminiraju pogreške nastale tijekom
pripreme uzorka za analizu. Optimalni unutarnji standard za tu svrhu jest izotopski označena verzija molekule koju
se želi kvantificirati, pri čemu se preferira upotreba deuterija zbog izobilja vodika u organskim molekulama. Glavni
cilj ovog istraživanja bio je optimizirati uvjete fragmentacije za deuterirani letrozol i deuterirani ribociklib koristeći
spektrometar masa s trostrukim kvadrupolom. Optimizacija je uključivala određivanje optimalnog fragmentorskog
napona, odabir fragmenata s najintenzivnijim signalom te određivanje optimalnih kolizijskih energija za generiranje
tih fragmenata. Pozitivna elektrosprej ionizacija deuteriranog letrozola formira molekulski ion s m/z 290,1. Optimalni
fragmentorski napon od 80 V daje najveći intenzitet signala tog molekulskog iona. Fragmenti m/z vrijednosti 194,2 i
221,0 najpogodniji su za analizu, s optimalnim kolizijskim energijama od 40 eV i 10 eV. Deuterirani ribociklib u
ionskom izvoru daje molekulski ion s m/z 441,2, pri čemu optimalni fragmentorski napon iznosi 160 V. Optimalni
fragmenti m/z 322,1, 252,2, 294,1 i 373,1 imaju najveći intenzitet signala pri kolizijskim energijama od 35 eV, 60
eV, 45 eV i 20 eV. Istraživanje je također pokazalo da je pozitivna elektrosprej ionizacija učinkovitija za analizu ovih
deuteriranih spojeva u usporedbi s negativnom elektrosprej ionizacijom jer generira fragmente s većim intenzitetom
signala.Ribociclib is an antineoplastic indicated for treating postmenopausal women with locally advanced or metastatic breast cancer that is HR-positive and HER2-negative. It is used in combination with hormone therapy that reduces the effect of estrogen, one such drug being letrozole (an aromatase inhibitor). During the development of bioanalytical methods for
therapeutic monitoring of these drugs, the use of internal standards is crucial to eliminate errors arising during sample
preparation for analysis. The optimal internal standard for this purpose is an isotopically labeled version of the molecule
to be quantified, with deuterium being preferred due to the abundance of hydrogen in organic molecules.The main aim of
this research was to optimize fragmentation conditions for deuterated letrozole and deuterated ribociclib using a triple
quadrupole mass spectrometer. Optimization involved determining the optimal fragmentor voltage, selecting the
fragments with the most intense signal, and determining the optimal collision energies to generate these fragments.
Positive electrospray ionization of deuterated letrozole forms a molecular ion with m/z 290.1. An optimal fragmentor
voltage of 80 V gives the highest signal intensity for this molecular ion. Fragments with m/z values of 194.2 and 221.0 are
most suitable for analysis, with optimal collision energies of 40 eV and 10 eV. Deuterated ribociclib in the ion source
gives a molecular ion with m/z 441.2, with an optimal fragmentor voltage of 160 V. Optimal fragments with m/z 322.1,
252.2, 294.1, and 373.1 have the highest signal intensity at collision energies of 35 eV, 60 eV, 45 eV, and 20 eV. The
research also showed that positive electrospray ionization is more effective for analyzing these deuterated compounds
compared to negative electrospray ionization, as it generates fragments with more intense signals
Dietary intake of selected vitamins among pharmacy students
Adekvatna, nutritivno raznolika prehrana nužna je za ostvarenje različitih dobrobiti koje pružaju pojedine namirnice. Vitamini su esencijalne komponente hrane koje se, budući da ih organizam ne može sam stvoriti, moraju unositi u određenim količinama, a razlikuju se po dostupnosti u namirnicama i topljivosti u vodi. Imaju iznimno važne funkcije za zdravlje te ukoliko ih u organizmu nema dovoljno, nastupaju bolesti. Zanimljiva skupina za praćenje unosa različitih vitamina su studenti, mlade osobe na putu prema osamostaljenju koje se nemaju vremena posvetiti prailnoj prehrani i aktivnom načinu života, budući da fakultet zahtjeva mnogo učenja i odricanja.
Ovaj rad temelji se na analizi nutritivnog unosa studenata treće godine Farmaceutsko-biokemijskog fakulteta u Zagrebu s naglaskom na unosu odabranih vitamina koji su se mogli obraditi iz dnevnika prehrane; vitamini skupine B (tiamin, riboflavin, niacin, piridoksin), vitamin C, vitamin A (retinoidi) i karotenoidi. Pomoću programa Prehrana analizirani su studentski dnevnici prehrane koji su se vodili tijekom četiri dana uz prethodne upute i napomene. U istraživanju prove-denom tijekom tri akademske godine (2020./2021., 2021./2022. i 2022./2023.) sudjelovalo je ukupno 382 ispitanika, od kojih je 99 muških (25,9 %) i 283 ženskih (74,1 %), prosječne dobii 21,5 godina. Program GraphPad Prism omogućio je statističku obradu podataka te je na temelju rezultata zaključeno da unos određenih vitamina poput tiamina, riboflavina i retinoida među populacijom studenata farmacije u Zagrebu nije zadovoljavajući. Dnevni unos piridoksina bio je u skladu sa preporučenim vrijednostima kod muške populacije, dok žene nisu uspjele zadovoljiti dnevne potrebe. S druge strane, unos vitamina C adekvatan je među ženama, za razliku od muškaraca koji ga nisu unijeli dovoljno. Niacin je jedini nutrijent čiji je unos adekvatan za oba spola. Unos karotenoida ne može se usporediti s preporučenim vrijednos-tima, budući da se oni ne definiraju kao esencijalni nutrijenti. Ovi rezultati pokazuju da studenti u potpunosti ne prakti-ciraju zdravu i uravnoteženu prehranu te je nužna bolja edukacija kako bi se povećala svijest o važnosti ovih mikronut-rijenata za cjelokupno zdravlje.Adequate, nutritionally diverse food intake is essential for achieving the various benefits provided by certain foods. Vitamins are essential components of food that, since the body cannot produce them on its own, must be consumed in specific amounts. They vary in availability in foods and water solubility. They play extremely important roles in health, and if the body lacks them, diseases may occur. An interesting group for monitoring vitamin intake are students—young individuals on the path to independence—who often do not have time to focus on a healthy diet and an active lifestyle, as university demands require a lot of studying and sacrifices.
This study is based on an analysis of the nutritional intake of third-year students at the Faculty of Pharmacy and Bioche-mistry in Zagreb, with a focus on the intake of certain vitamins that could be assessed from dietary diaries: B vitamins (thiamine, riboflavin, niacin, pyridoxine), vitamin C, vitamin A (retinoids) and carotenoids. The students' dietary diaries, which were kept for four days with prior instructions and guidelines, were analysed using the "Prehrana" software. A total of 382 participants took part in the study, conducted over three academic years (2020./2021., 2021./2022., and 2022./2023.), of whom 99 were male (25.9%) and 283 female participants (74.1%), with an average age of 21.5 years. The GraphPad Prism program enabled statistical processing of the data, and based on the results, it was concluded that the intake of certain vitamins, such as thiamine, riboflavin, and retinoids, among the pharmacy student population in Zagreb, was not satisfactory. The daily intake of pyridoxine met the recommended values for the male population, while women did not meet the daily requirements. On the other hand, vitamin C intake is adequate among women, unlike men, who have not consumed sufficient amounts. Niacin is the only nutrient with adequate intake for both genders. Carotenoid intake cannot be compared to recommended values, as they are not defined as essential nutrients. These results show that students do not fully practice healthy and balanced eating habits, and better education is necessary to raise awareness of the importance of these micronutrients for overall health