TY  - JOUR
AU  - Milosavljević, Filip
AU  - Molden, Espen
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5593
AB  - The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.
PB  - Elsevier B.V.
T2  - European Neuropsychopharmacology
T1  - Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials
VL  - 81
SP  - 43
EP  - 52
DO  - 10.1016/j.euroneuro.2024.01.005
ER  - 

@article{
author = "Milosavljević, Filip and Molden, Espen and Ingelman-Sundberg, Magnus and Jukić, Marin",
year = "2024",
abstract = "The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.",
publisher = "Elsevier B.V.",
journal = "European Neuropsychopharmacology",
title = "Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials",
volume = "81",
pages = "43-52",
doi = "10.1016/j.euroneuro.2024.01.005"
}

Milosavljević, F., Molden, E., Ingelman-Sundberg, M.,& Jukić, M.. (2024). Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials. in European Neuropsychopharmacology
Elsevier B.V.., 81, 43-52.
https://doi.org/10.1016/j.euroneuro.2024.01.005

Milosavljević F, Molden E, Ingelman-Sundberg M, Jukić M. Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials. in European Neuropsychopharmacology. 2024;81:43-52.
doi:10.1016/j.euroneuro.2024.01.005 .

Milosavljević, Filip, Molden, Espen, Ingelman-Sundberg, Magnus, Jukić, Marin, "Current level of evidence for improvement of antidepressant efficacy and
tolerability by pharmacogenomic-guided treatment: A Systematic review
and meta-analysis of randomized controlled clinical trials" in European Neuropsychopharmacology, 81 (2024):43-52,
https://doi.org/10.1016/j.euroneuro.2024.01.005 . .

TY  - JOUR
AU  - Jukić, Marin
AU  - Milosavljević, Filip
AU  - Molden, Espen
AU  - Ingelman-Sundberg, Magnus
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4307
AB  - Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent large studies indicate a true benefit and cost-effectiveness of pre-emptive genotyping for more successful psychotherapy. However, it is apparent that we still lack knowledge of many additional heritable genetic factors of importance for explanation of the interindividual differences in response to psychiatric drugs. Thus, more effort to further develop pharmacogenomic psychiatry should be invested to achieve a broader clinical implementation.
PB  - Elsevier Ltd
T2  - Trends in Pharmacological Sciences
T1  - Pharmacogenomics in treatment of depression and psychosis: an update
VL  - 43
IS  - 12
SP  - 1055
EP  - 1069
DO  - 10.1016/j.tips.2022.09.011
ER  - 

@article{
author = "Jukić, Marin and Milosavljević, Filip and Molden, Espen and Ingelman-Sundberg, Magnus",
year = "2022",
abstract = "Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent large studies indicate a true benefit and cost-effectiveness of pre-emptive genotyping for more successful psychotherapy. However, it is apparent that we still lack knowledge of many additional heritable genetic factors of importance for explanation of the interindividual differences in response to psychiatric drugs. Thus, more effort to further develop pharmacogenomic psychiatry should be invested to achieve a broader clinical implementation.",
publisher = "Elsevier Ltd",
journal = "Trends in Pharmacological Sciences",
title = "Pharmacogenomics in treatment of depression and psychosis: an update",
volume = "43",
number = "12",
pages = "1055-1069",
doi = "10.1016/j.tips.2022.09.011"
}

Jukić, M., Milosavljević, F., Molden, E.,& Ingelman-Sundberg, M.. (2022). Pharmacogenomics in treatment of depression and psychosis: an update. in Trends in Pharmacological Sciences
Elsevier Ltd., 43(12), 1055-1069.
https://doi.org/10.1016/j.tips.2022.09.011

Jukić M, Milosavljević F, Molden E, Ingelman-Sundberg M. Pharmacogenomics in treatment of depression and psychosis: an update. in Trends in Pharmacological Sciences. 2022;43(12):1055-1069.
doi:10.1016/j.tips.2022.09.011 .

Jukić, Marin, Milosavljević, Filip, Molden, Espen, Ingelman-Sundberg, Magnus, "Pharmacogenomics in treatment of depression and psychosis: an update" in Trends in Pharmacological Sciences, 43, no. 12 (2022):1055-1069,
https://doi.org/10.1016/j.tips.2022.09.011 . .

TY  - JOUR
AU  - Joković, Danilo
AU  - Milosavljević, Filip
AU  - Stojanović, Zvezdana
AU  - Šupić, Gordana
AU  - Vojvodić, Danilo
AU  - Uzelac, Bojana
AU  - Jukić, Marin
AU  - Petković Ćurčin, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4080
AB  - The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow- up. The primary efficacy measurement was the change from baseline in Hamilton’s Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No sig- nificant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.
PB  - Elsevier Ireland Ltd
T2  - Psychiatry Research
T1  - CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability
VL  - 312
DO  - 10.1016/j.psychres.2022.114535
ER  - 

@article{
author = "Joković, Danilo and Milosavljević, Filip and Stojanović, Zvezdana and Šupić, Gordana and Vojvodić, Danilo and Uzelac, Bojana and Jukić, Marin and Petković Ćurčin, Aleksandra",
year = "2022",
abstract = "The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow- up. The primary efficacy measurement was the change from baseline in Hamilton’s Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No sig- nificant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.",
publisher = "Elsevier Ireland Ltd",
journal = "Psychiatry Research",
title = "CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability",
volume = "312",
doi = "10.1016/j.psychres.2022.114535"
}

Joković, D., Milosavljević, F., Stojanović, Z., Šupić, G., Vojvodić, D., Uzelac, B., Jukić, M.,& Petković Ćurčin, A.. (2022). CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability. in Psychiatry Research
Elsevier Ireland Ltd., 312.
https://doi.org/10.1016/j.psychres.2022.114535

Joković D, Milosavljević F, Stojanović Z, Šupić G, Vojvodić D, Uzelac B, Jukić M, Petković Ćurčin A. CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability. in Psychiatry Research. 2022;312.
doi:10.1016/j.psychres.2022.114535 .

Joković, Danilo, Milosavljević, Filip, Stojanović, Zvezdana, Šupić, Gordana, Vojvodić, Danilo, Uzelac, Bojana, Jukić, Marin, Petković Ćurčin, Aleksandra, "CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability" in Psychiatry Research, 312 (2022),
https://doi.org/10.1016/j.psychres.2022.114535 . .

TY  - JOUR
AU  - Jeremić, Aleksandra
AU  - Milosavljević, Filip
AU  - Opanković, Ana
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4305
AB  - The use of antidepressants has been steadily increasing. Even though the amount of evidence on the usefulness of personalized drug dosing in depression treatment is growing, there is still resistance and skepticism among physicians and regulators regarding the implementation of CYP450 genotyping and therapeutic drug monitoring in psychiatric clinical practice. The aim of this study was to quantify the opinions of psychiatrists and patients from three large psychiatric clinics in Belgrade, Serbia, and to examine what requirements need to be met to make changes in clinical guidelines or recommendations. All participants completed an anonymous questionnaire that was developed at the Faculty of Pharmacy, University of Belgrade. Fourteen practicing psychiatrists and 30 patients currently treated for depression completed the questionnaire. Distributions of opinion scores were compared between the psychiatrists and patients upon the visual inspection of the violin plots. Our results show that psychiatrists predominantly have a positive opinion on personalized dosing in psychiatry and that patients are most likely to comply with new approaches in depression pharmacotherapy. However, due to the long time needed for regulatory change, it is very unlikely that personalized dosing would be rapidly implemented in clinical practice, even if adequate evidence was to emerge.
AB  - Upotreba antidepresiva je u stalnom porastu. Iako raste količina dokaza o korisnosti personalizovanog doziranja lekova u lečenju depresije, još uvek postoji veliki otpor i skepticizam među lekarima i regulatorima u pogledu primene CYP450 genotipizacije i terapijskog praćenja lekova u psihijatrijskoj kliničkoj praksi. Cilj ove studije je bio da se kvantifikuju mišljenja psihijatara i pacijenata sa tri velike psihijatrijske klinike u Beogradu, u Srbiji, i da se ispita koji zahtevi treba da budu ispunjeni da bi se izvršile promene u kliničkim smernicama ili preporukama za doziranje antidepresiva. Svi učesnici su popunili anonimni upitnik koji je izrađen na Farmaceutskom fakultetu Univerziteta u Beogradu. Upitnik je popunilo 44 učesnika, od kojih 14 psihijatara i 30 pacijenata koji se trenutno leče od depresije. Dodatno je kontaktiran i jedan stručnjak za farmakologiju. Distribucija ocena mišljenja je poređena između psihijatara i pacijenata nakon vizuelnog pregleda violina dijagrama. Naši rezultati pokazuju da psihijatri uglavnom imaju pozitivno mišljenje o personalizovanom doziranju u psihijatriji i da bi se pacijenti većinski pridržavali novih pristupa u farmakoterapiji depresije. Međutim, malo je verovatno da bi regulatorna tela u Srbiji brzo ažurirala svoje smernice, čak i ako bi se pojavili adekvatni dokazi.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Patients’ and psychiatrists’ stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects
T1  - Stav pacijenata i psihijatara o trenutnom stanju farmakoterapije depresije u Srbiji i mogućnosti uvođenja personalizovane farmakoterapije i njenim potencijalnim efektima
VL  - 72
IS  - 4
SP  - 381
EP  - 391
DO  - 10.5937/arhfarm72-37613
ER  - 

@article{
author = "Jeremić, Aleksandra and Milosavljević, Filip and Opanković, Ana and Jukić, Marin",
year = "2022",
abstract = "The use of antidepressants has been steadily increasing. Even though the amount of evidence on the usefulness of personalized drug dosing in depression treatment is growing, there is still resistance and skepticism among physicians and regulators regarding the implementation of CYP450 genotyping and therapeutic drug monitoring in psychiatric clinical practice. The aim of this study was to quantify the opinions of psychiatrists and patients from three large psychiatric clinics in Belgrade, Serbia, and to examine what requirements need to be met to make changes in clinical guidelines or recommendations. All participants completed an anonymous questionnaire that was developed at the Faculty of Pharmacy, University of Belgrade. Fourteen practicing psychiatrists and 30 patients currently treated for depression completed the questionnaire. Distributions of opinion scores were compared between the psychiatrists and patients upon the visual inspection of the violin plots. Our results show that psychiatrists predominantly have a positive opinion on personalized dosing in psychiatry and that patients are most likely to comply with new approaches in depression pharmacotherapy. However, due to the long time needed for regulatory change, it is very unlikely that personalized dosing would be rapidly implemented in clinical practice, even if adequate evidence was to emerge., Upotreba antidepresiva je u stalnom porastu. Iako raste količina dokaza o korisnosti personalizovanog doziranja lekova u lečenju depresije, još uvek postoji veliki otpor i skepticizam među lekarima i regulatorima u pogledu primene CYP450 genotipizacije i terapijskog praćenja lekova u psihijatrijskoj kliničkoj praksi. Cilj ove studije je bio da se kvantifikuju mišljenja psihijatara i pacijenata sa tri velike psihijatrijske klinike u Beogradu, u Srbiji, i da se ispita koji zahtevi treba da budu ispunjeni da bi se izvršile promene u kliničkim smernicama ili preporukama za doziranje antidepresiva. Svi učesnici su popunili anonimni upitnik koji je izrađen na Farmaceutskom fakultetu Univerziteta u Beogradu. Upitnik je popunilo 44 učesnika, od kojih 14 psihijatara i 30 pacijenata koji se trenutno leče od depresije. Dodatno je kontaktiran i jedan stručnjak za farmakologiju. Distribucija ocena mišljenja je poređena između psihijatara i pacijenata nakon vizuelnog pregleda violina dijagrama. Naši rezultati pokazuju da psihijatri uglavnom imaju pozitivno mišljenje o personalizovanom doziranju u psihijatriji i da bi se pacijenti većinski pridržavali novih pristupa u farmakoterapiji depresije. Međutim, malo je verovatno da bi regulatorna tela u Srbiji brzo ažurirala svoje smernice, čak i ako bi se pojavili adekvatni dokazi.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Patients’ and psychiatrists’ stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects, Stav pacijenata i psihijatara o trenutnom stanju farmakoterapije depresije u Srbiji i mogućnosti uvođenja personalizovane farmakoterapije i njenim potencijalnim efektima",
volume = "72",
number = "4",
pages = "381-391",
doi = "10.5937/arhfarm72-37613"
}

Jeremić, A., Milosavljević, F., Opanković, A.,& Jukić, M.. (2022). Patients’ and psychiatrists’ stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(4), 381-391.
https://doi.org/10.5937/arhfarm72-37613

Jeremić A, Milosavljević F, Opanković A, Jukić M. Patients’ and psychiatrists’ stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects. in Arhiv za farmaciju. 2022;72(4):381-391.
doi:10.5937/arhfarm72-37613 .

Jeremić, Aleksandra, Milosavljević, Filip, Opanković, Ana, Jukić, Marin, "Patients’ and psychiatrists’ stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects" in Arhiv za farmaciju, 72, no. 4 (2022):381-391,
https://doi.org/10.5937/arhfarm72-37613 . .

TY  - JOUR
AU  - Jeremić, Aleksandra
AU  - Milosavljević, Filip
AU  - Vladimirov, Sandra
AU  - Batinić, Bojan
AU  - Marković, Bojan
AU  - Jukić, Marin
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4733
AB  - Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes).
AB  - Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).
T2  - Arhiv za farmaciju
T1  - Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma
T1  - Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi
VL  - 71
IS  - 5
SP  - 365
EP  - 377
DO  - 10.5937/arhfarm71-31163
ER  - 

@article{
author = "Jeremić, Aleksandra and Milosavljević, Filip and Vladimirov, Sandra and Batinić, Bojan and Marković, Bojan and Jukić, Marin",
year = "2021",
abstract = "Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes)., Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).",
journal = "Arhiv za farmaciju",
title = "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma, Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi",
volume = "71",
number = "5",
pages = "365-377",
doi = "10.5937/arhfarm71-31163"
}

Jeremić, A., Milosavljević, F., Vladimirov, S., Batinić, B., Marković, B.,& Jukić, M.. (2021). Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju, 71(5), 365-377.
https://doi.org/10.5937/arhfarm71-31163

Jeremić A, Milosavljević F, Vladimirov S, Batinić B, Marković B, Jukić M. Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju. 2021;71(5):365-377.
doi:10.5937/arhfarm71-31163 .

Jeremić, Aleksandra, Milosavljević, Filip, Vladimirov, Sandra, Batinić, Bojan, Marković, Bojan, Jukić, Marin, "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma" in Arhiv za farmaciju, 71, no. 5 (2021):365-377,
https://doi.org/10.5937/arhfarm71-31163 . .