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  - CONF
AU  - Vuković, Petar
AU  - Jeremić, Aleksandra
AU  - Vezmar, Milica
AU  - Pešić, Danilo
AU  - Drakulić, Jelena
AU  - Milosavljević, Filip
AU  - Miljević, Čedo
AU  - Marić-Bojović, Nađa
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4732
AB  - Background: Considering the negative impact of anxiety and depression on society and lack of emergence of new antidepressants, it is of paramount importance to utilize the available treatment options in the best manner possible. Escitalopram is a commonly prescribed antidepressant that is predominantly metabolized by the polymorphic CYP2C19 liver enzyme and consequently, CYP2C19 genotype affects escitalopram metabolism. Previous report showed a strong association between CYP2C19 genotype and escitalopram exposure [1]; therefore, CYP2C19 genotype is a potentially clinically relevant feature in escitalopram treatment, since underdosed patients exhibit lower escitalopram treatment effectiveness [2] and since escitalopram adverse drug reactions (ADR) are dose dependent [3]. Objective of this prospective cohort clinical trial is to evaluate the impact of escitalopram dose adjustment based on escitalopram exposure on treatment efficacy and safety.

Methods: In this prospective cohort study patients suffering from depression were assessed for potential clinical benefits of a personalized dosing regimen for escitalopram, which is based on therapeutic drug monitoring of escitalopram plasma level. Treatment effectiveness was evaluated based on Hamilton depression rating scale (HAM-D), which was performed one day prior to escitalopram treatment initiation (Baseline, Visit 0), as well as after four (Visit 1) and eight (Visit 2) weeks of follow-up. Side effect assessment was based on Scandinavian UKU Side effects rating scale, which was performed at V1 and V2. In case of need, dose adjustment was performed at V1 and was guided by the measured steady state drug plasma level using HPLC two weeks after treatment initiation, with the aim to achieve the optimal exposure to escitalopram in every patient at V2. Relative change in HAM-D and UKU scale readouts from V1 to V2, were compared between comparator (dose was adjusted) and control (dose was not adjusted) groups by independent samples t-test and Chi-square test, respectively. The study protocol in full detail is available on clincaltrials.gov [4]

Results: To this day, 25 participants completed the study, and out of these, 19 participants required dose adjustment between visits. There were no statistically significant differences in the change in HAM-D scores from V1 to V2 between groups (p>0.1). In the comparator group, 11/19 patients reported ADRs, compared to 2/6 patients in control group. Appearance of new, or worsening of the existing ADRs between V1 and V2 was reported in 6/19 patients in the comparator group and in 1/6 patients in the control group. There was no statistically significant difference between groups in ADR emergence or worsening (p>0.1)

Conclusion: The dose of escitalopram in 19 participants was augmented, but did not show statistically significant improvement in treatment effectiveness when compared to control group. There was no statistically significant increase in ADR frequencies in the dose augmentation group either, which is in concordance with the hypothesis that dose increase in underdosed patients does not lead to the increase of ADR frequency and severity. Noteworthy, since this report represents interim analysis on a sample which is approximately one fourth of the planned cohort, the conclusions are not yet unequivocal.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Effects of personalized dosing based on drug plasma level quantification on effectiveness and safety of escitalopram treatment
VL  - 1
IS  - Supplement 2
SP  - 331
EP  - 332
DO  - 10.1016/j.nsa.2022.100765
ER  - 

@conference{
author = "Vuković, Petar and Jeremić, Aleksandra and Vezmar, Milica and Pešić, Danilo and Drakulić, Jelena and Milosavljević, Filip and Miljević, Čedo and Marić-Bojović, Nađa and Jukić, Marin",
year = "2022",
abstract = "Background: Considering the negative impact of anxiety and depression on society and lack of emergence of new antidepressants, it is of paramount importance to utilize the available treatment options in the best manner possible. Escitalopram is a commonly prescribed antidepressant that is predominantly metabolized by the polymorphic CYP2C19 liver enzyme and consequently, CYP2C19 genotype affects escitalopram metabolism. Previous report showed a strong association between CYP2C19 genotype and escitalopram exposure [1]; therefore, CYP2C19 genotype is a potentially clinically relevant feature in escitalopram treatment, since underdosed patients exhibit lower escitalopram treatment effectiveness [2] and since escitalopram adverse drug reactions (ADR) are dose dependent [3]. Objective of this prospective cohort clinical trial is to evaluate the impact of escitalopram dose adjustment based on escitalopram exposure on treatment efficacy and safety.

Methods: In this prospective cohort study patients suffering from depression were assessed for potential clinical benefits of a personalized dosing regimen for escitalopram, which is based on therapeutic drug monitoring of escitalopram plasma level. Treatment effectiveness was evaluated based on Hamilton depression rating scale (HAM-D), which was performed one day prior to escitalopram treatment initiation (Baseline, Visit 0), as well as after four (Visit 1) and eight (Visit 2) weeks of follow-up. Side effect assessment was based on Scandinavian UKU Side effects rating scale, which was performed at V1 and V2. In case of need, dose adjustment was performed at V1 and was guided by the measured steady state drug plasma level using HPLC two weeks after treatment initiation, with the aim to achieve the optimal exposure to escitalopram in every patient at V2. Relative change in HAM-D and UKU scale readouts from V1 to V2, were compared between comparator (dose was adjusted) and control (dose was not adjusted) groups by independent samples t-test and Chi-square test, respectively. The study protocol in full detail is available on clincaltrials.gov [4]

Results: To this day, 25 participants completed the study, and out of these, 19 participants required dose adjustment between visits. There were no statistically significant differences in the change in HAM-D scores from V1 to V2 between groups (p>0.1). In the comparator group, 11/19 patients reported ADRs, compared to 2/6 patients in control group. Appearance of new, or worsening of the existing ADRs between V1 and V2 was reported in 6/19 patients in the comparator group and in 1/6 patients in the control group. There was no statistically significant difference between groups in ADR emergence or worsening (p>0.1)

Conclusion: The dose of escitalopram in 19 participants was augmented, but did not show statistically significant improvement in treatment effectiveness when compared to control group. There was no statistically significant increase in ADR frequencies in the dose augmentation group either, which is in concordance with the hypothesis that dose increase in underdosed patients does not lead to the increase of ADR frequency and severity. Noteworthy, since this report represents interim analysis on a sample which is approximately one fourth of the planned cohort, the conclusions are not yet unequivocal.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Effects of personalized dosing based on drug plasma level quantification on effectiveness and safety of escitalopram treatment",
volume = "1",
number = "Supplement 2",
pages = "331-332",
doi = "10.1016/j.nsa.2022.100765"
}

Vuković, P., Jeremić, A., Vezmar, M., Pešić, D., Drakulić, J., Milosavljević, F., Miljević, Č., Marić-Bojović, N.,& Jukić, M.. (2022). Effects of personalized dosing based on drug plasma level quantification on effectiveness and safety of escitalopram treatment. in Neuroscience Applied
Elsevier., 1(Supplement 2), 331-332.
https://doi.org/10.1016/j.nsa.2022.100765

Vuković P, Jeremić A, Vezmar M, Pešić D, Drakulić J, Milosavljević F, Miljević Č, Marić-Bojović N, Jukić M. Effects of personalized dosing based on drug plasma level quantification on effectiveness and safety of escitalopram treatment. in Neuroscience Applied. 2022;1(Supplement 2):331-332.
doi:10.1016/j.nsa.2022.100765 .

Vuković, Petar, Jeremić, Aleksandra, Vezmar, Milica, Pešić, Danilo, Drakulić, Jelena, Milosavljević, Filip, Miljević, Čedo, Marić-Bojović, Nađa, Jukić, Marin, "Effects of personalized dosing based on drug plasma level quantification on effectiveness and safety of escitalopram treatment" in Neuroscience Applied, 1, no. Supplement 2 (2022):331-332,
https://doi.org/10.1016/j.nsa.2022.100765 . .

TY  - CONF
AU  - Jeremić, Aleksandra
AU  - Vuković, Petar
AU  - Vezmar, Milica
AU  - Pešić, Danilo
AU  - Drakulić, Jelena
AU  - Milosavljević, Filip
AU  - Miljević, Čedo
AU  - Marković, Bojan
AU  - Marić-Bojović, Nađa
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4731
AB  - Background: Depression causes significant burden to the society world-wide. Escitalopram is a commonly prescribed antidepressant, predominantly metabolized by the polymorphic CYP2C19 enzyme; however, this drug isn’t always effective [1]. The CYP2C19 genotype determines the CYP2C19 enzymatic capacity and CYP2C19*2 is the main loss-of-function (Null) allele [2]. In the most psychiatric clinics worldwide, escitalopram therapy usually starts with the standard recommended dose of 10 mg/day, regardless of CYP2C19 genotype [3]. The objective of this study was the quantification of difference in the escitalopram exposure among patients between genetically associated CYP2C19 slow and normal metabolizers, considering also the body weight [4].

Methods: In this ongoing prospective cross sectional study, the drug concentration was measured in 53 outpatients treated with 10 mg of escitalopram, 2 weeks after treatment initiation, 24 hours after the last dose. Measured plasma concentration was 25-50 ng/ml was considered the ideal drug exposure. [5] If the drug concentration was 5-25 ng/ml, patients were classified as underdosed/underexposed, while patients with drug concentration <5ng/ml were classified as non-compliers and excluded from the further analysis. Patients were genotyped by polymerase chain reaction–based assay for the CYP2C19*2 allele. All participants were included from the Institute for Mental Health in Belgrade outpatient clinic and daily hospital. The patients were classified based on their CYP2C19 genotype; those carrying CYP2C19*2 variant alleles were categorized into slow metabolizer group, while non-carriers were categorized into normal metabolizer group. Difference in body weight and age between slow and metabolizer groups was analysed by the Mann-Whitney’s test. The effects of CYP2C19 metabolizer category (normal vs. slow metabolizer) and body weight on escitalopram plasma level were evaluated by the linear regression model.

Results: Out of 53 outpatients, who completed the study to date, 24 participants were slow metabolizers and 29 participants were normal metabolizers. After two weeks of treatment with 10mg of escitalopram, only 13 patients (24%) were within the therapeutic range (25-50ng/ml), no patient was underexposed, while the remaining 40 patients were underexposed. Median age body weight in the slow metabolizers group were 41 years [IQR: 27-47] and 77kg [IQR: 65-88,5], while in normal metabolizers group age and body weight were 35 years [IQR: 22-49] and 66kg [IQR: 59-88]. The drug level increase due to lower body weight and due to occurrence of CYP2C19*2 allele observed in the regression equation did not reach statistical significance.

Conclusion: While the result directionality was in accordance with the previously published studies, the effects of body weight and CYP2C19*2 allele occurrence were not significant in the analysed cohort. The absence of significant effects was likely due to still limited power of the study. Since this interim analysis includes only approximately one third of patients compared with what had been originally planned, it is expected that firmer conclusions related to the combined effect of CYP2C19 genotype and body weight on escitalopram exposure will emerge after all planned patients are included.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study
VL  - 1
IS  - Supplement 2
SP  - 330
EP  - 331
DO  - 10.1016/j.nsa.2022.100763
ER  - 

@conference{
author = "Jeremić, Aleksandra and Vuković, Petar and Vezmar, Milica and Pešić, Danilo and Drakulić, Jelena and Milosavljević, Filip and Miljević, Čedo and Marković, Bojan and Marić-Bojović, Nađa and Jukić, Marin",
year = "2022",
abstract = "Background: Depression causes significant burden to the society world-wide. Escitalopram is a commonly prescribed antidepressant, predominantly metabolized by the polymorphic CYP2C19 enzyme; however, this drug isn’t always effective [1]. The CYP2C19 genotype determines the CYP2C19 enzymatic capacity and CYP2C19*2 is the main loss-of-function (Null) allele [2]. In the most psychiatric clinics worldwide, escitalopram therapy usually starts with the standard recommended dose of 10 mg/day, regardless of CYP2C19 genotype [3]. The objective of this study was the quantification of difference in the escitalopram exposure among patients between genetically associated CYP2C19 slow and normal metabolizers, considering also the body weight [4].

Methods: In this ongoing prospective cross sectional study, the drug concentration was measured in 53 outpatients treated with 10 mg of escitalopram, 2 weeks after treatment initiation, 24 hours after the last dose. Measured plasma concentration was 25-50 ng/ml was considered the ideal drug exposure. [5] If the drug concentration was 5-25 ng/ml, patients were classified as underdosed/underexposed, while patients with drug concentration <5ng/ml were classified as non-compliers and excluded from the further analysis. Patients were genotyped by polymerase chain reaction–based assay for the CYP2C19*2 allele. All participants were included from the Institute for Mental Health in Belgrade outpatient clinic and daily hospital. The patients were classified based on their CYP2C19 genotype; those carrying CYP2C19*2 variant alleles were categorized into slow metabolizer group, while non-carriers were categorized into normal metabolizer group. Difference in body weight and age between slow and metabolizer groups was analysed by the Mann-Whitney’s test. The effects of CYP2C19 metabolizer category (normal vs. slow metabolizer) and body weight on escitalopram plasma level were evaluated by the linear regression model.

Results: Out of 53 outpatients, who completed the study to date, 24 participants were slow metabolizers and 29 participants were normal metabolizers. After two weeks of treatment with 10mg of escitalopram, only 13 patients (24%) were within the therapeutic range (25-50ng/ml), no patient was underexposed, while the remaining 40 patients were underexposed. Median age body weight in the slow metabolizers group were 41 years [IQR: 27-47] and 77kg [IQR: 65-88,5], while in normal metabolizers group age and body weight were 35 years [IQR: 22-49] and 66kg [IQR: 59-88]. The drug level increase due to lower body weight and due to occurrence of CYP2C19*2 allele observed in the regression equation did not reach statistical significance.

Conclusion: While the result directionality was in accordance with the previously published studies, the effects of body weight and CYP2C19*2 allele occurrence were not significant in the analysed cohort. The absence of significant effects was likely due to still limited power of the study. Since this interim analysis includes only approximately one third of patients compared with what had been originally planned, it is expected that firmer conclusions related to the combined effect of CYP2C19 genotype and body weight on escitalopram exposure will emerge after all planned patients are included.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study",
volume = "1",
number = "Supplement 2",
pages = "330-331",
doi = "10.1016/j.nsa.2022.100763"
}

Jeremić, A., Vuković, P., Vezmar, M., Pešić, D., Drakulić, J., Milosavljević, F., Miljević, Č., Marković, B., Marić-Bojović, N.,& Jukić, M.. (2022). Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study. in Neuroscience Applied
Elsevier., 1(Supplement 2), 330-331.
https://doi.org/10.1016/j.nsa.2022.100763

Jeremić A, Vuković P, Vezmar M, Pešić D, Drakulić J, Milosavljević F, Miljević Č, Marković B, Marić-Bojović N, Jukić M. Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study. in Neuroscience Applied. 2022;1(Supplement 2):330-331.
doi:10.1016/j.nsa.2022.100763 .

Jeremić, Aleksandra, Vuković, Petar, Vezmar, Milica, Pešić, Danilo, Drakulić, Jelena, Milosavljević, Filip, Miljević, Čedo, Marković, Bojan, Marić-Bojović, Nađa, Jukić, Marin, "Association between CYP2C19 genotype and body weight with escitalopram exposure – a cross sectional study" in Neuroscience Applied, 1, no. Supplement 2 (2022):330-331,
https://doi.org/10.1016/j.nsa.2022.100763 . .

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 . .