TY  - JOUR
AU  - Milosavljević, Filip
AU  - Brusini, Irene
AU  - Atanasov, Andrea
AU  - Manojlović, Marina
AU  - Vučić, Marija
AU  - Oreščanin-Dušić, Zorana
AU  - Brkljačić, Jelena
AU  - Miljević, Čedo
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Wang, Chunliang
AU  - Damberg, Peter
AU  - Pešić, Vesna
AU  - Tyndale, Rachel F.
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4516
AB  - Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia. Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride. Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice. Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.
PB  - John Wiley and Sons Inc
T2  - Neuropathology and Applied Neurobiology
T1  - The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia
VL  - 49
IS  - 1
DO  - 10.1111/nan.12867
ER  - 

@article{
author = "Milosavljević, Filip and Brusini, Irene and Atanasov, Andrea and Manojlović, Marina and Vučić, Marija and Oreščanin-Dušić, Zorana and Brkljačić, Jelena and Miljević, Čedo and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Wang, Chunliang and Damberg, Peter and Pešić, Vesna and Tyndale, Rachel F. and Ingelman-Sundberg, Magnus and Jukić, Marin",
year = "2023",
abstract = "Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia. Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride. Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice. Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.",
publisher = "John Wiley and Sons Inc",
journal = "Neuropathology and Applied Neurobiology",
title = "The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia",
volume = "49",
number = "1",
doi = "10.1111/nan.12867"
}

Milosavljević, F., Brusini, I., Atanasov, A., Manojlović, M., Vučić, M., Oreščanin-Dušić, Z., Brkljačić, J., Miljević, Č., Nikolić-Kokić, A., Blagojević, D., Wang, C., Damberg, P., Pešić, V., Tyndale, R. F., Ingelman-Sundberg, M.,& Jukić, M.. (2023). The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia. in Neuropathology and Applied Neurobiology
John Wiley and Sons Inc., 49(1).
https://doi.org/10.1111/nan.12867

Milosavljević F, Brusini I, Atanasov A, Manojlović M, Vučić M, Oreščanin-Dušić Z, Brkljačić J, Miljević Č, Nikolić-Kokić A, Blagojević D, Wang C, Damberg P, Pešić V, Tyndale RF, Ingelman-Sundberg M, Jukić M. The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia. in Neuropathology and Applied Neurobiology. 2023;49(1).
doi:10.1111/nan.12867 .

Milosavljević, Filip, Brusini, Irene, Atanasov, Andrea, Manojlović, Marina, Vučić, Marija, Oreščanin-Dušić, Zorana, Brkljačić, Jelena, Miljević, Čedo, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Wang, Chunliang, Damberg, Peter, Pešić, Vesna, Tyndale, Rachel F., Ingelman-Sundberg, Magnus, Jukić, Marin, "The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia" in Neuropathology and Applied Neurobiology, 49, no. 1 (2023),
https://doi.org/10.1111/nan.12867 . .

TY  - CONF
AU  - Manojlović, Marina
AU  - Milosavljević, Filip
AU  - Atanasov, Andrea
AU  - Batinić, Bojan
AU  - Sitarica, Pavle
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4728
AB  - Background: Due to the COVID-19 pandemic, the prevalence of anxiety and
depression disorders increased by approximately 25-30% [1]. Reasons behind
this are likely associated with the increased average daily level of stress, especially during social isolation. Since one of the main adolescence hallmarks is
formation of meaningful social and love relationships, it represents a particularly
vulnerable period for social stress [2]. The aim of this study was to evaluate
whether isolation stress during the adolescence causes general and social anxiety
in rats.
Methods: Sprague-Dawley rats of both sexes were used for the adolescence social
isolation experiment. From the fourth postnatal week, 24 rats were single caged
and therefore subjected to the social isolation stress, while 24 non-stressed
control rats remained in groups of four per cage and were handled three times a
week. All rats were handled daily for one week and weighted before behavioural
tests. From eleventh week, rats were subjected to the open field, elevated plus
maze, and three-chamber sociability tests, with two-day gap between different
tests. In open field test, time spent in the centre was measured, while in the
elevated plus maze test, the time spent in open arms, normalized to time spent in
all arms was measured; reduction in values of these parameters was interpreted
as general anxiety. In the social preference test, social preference ratio was
calculated for each animal, according to the previously published protocol [3],
and reduction in this ratio was interpreted as social anxiety. 2-way ANOVA, with
sex and isolation stress as factors, was used for parametric data analysis, and
Fischer’s post hoc test was used to detect statistically significant between group
differences. Kruskal-Wallis test was used for non-parametric data analysis, and
Mann-Whitney post hoc test with multiple comparison correction was used to
detect statistically significant between group differences.
Results: Compared to control rats, time spent in the centre of open field (-44%
[95%CI: -76%, -12%] p¼0,008) and total distance travelled (-17% [95%CI:
-32%, -2%], p¼0.028) were decreased in isolated males, but not in females
(p>0.1). In elevated plus maze test, time spent in the open arms was significantly
decreased in male isolated rats (isolated: [median: 0.76, IQR: 0.00 – 2.06] vs
control: [median: 4.96, IQR: 2.04 – 17.75], p¼0.034); however, this change did
not remain significant after multiple comparisons corrections. In sociability tests,
both male and female isolated rats exhibited increase in social preference ratio
(+32% [95%CI: 12%, 51%], p¼0.002) and preference for novel animal over
familiar one (+48% [95%CI: 10%, 86%], p¼0.015), compared to control rats.
Body weight, measured after six weeks of social isolation at week ten, was
increased in isolated male compared to control rats (+19% [95%CI: 14%, 24%],
p<0.001), while there was no such difference observed in female rats.
Conclusion: Social isolation caused increase in general anxiety in male, but not
female rats. In addition, both male and female rats exhibited robust increase in
preference for social interaction and novel social stimulus, which is the result
opposite from the expected social anxiety as initially hypothesized.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats
VL  - 1
IS  - Supplement 2
SP  - 19
EP  - 19
DO  - 10.1016/j.nsa.2022.100149
ER  - 

@conference{
author = "Manojlović, Marina and Milosavljević, Filip and Atanasov, Andrea and Batinić, Bojan and Sitarica, Pavle and Jukić, Marin",
year = "2022",
abstract = "Background: Due to the COVID-19 pandemic, the prevalence of anxiety and
depression disorders increased by approximately 25-30% [1]. Reasons behind
this are likely associated with the increased average daily level of stress, especially during social isolation. Since one of the main adolescence hallmarks is
formation of meaningful social and love relationships, it represents a particularly
vulnerable period for social stress [2]. The aim of this study was to evaluate
whether isolation stress during the adolescence causes general and social anxiety
in rats.
Methods: Sprague-Dawley rats of both sexes were used for the adolescence social
isolation experiment. From the fourth postnatal week, 24 rats were single caged
and therefore subjected to the social isolation stress, while 24 non-stressed
control rats remained in groups of four per cage and were handled three times a
week. All rats were handled daily for one week and weighted before behavioural
tests. From eleventh week, rats were subjected to the open field, elevated plus
maze, and three-chamber sociability tests, with two-day gap between different
tests. In open field test, time spent in the centre was measured, while in the
elevated plus maze test, the time spent in open arms, normalized to time spent in
all arms was measured; reduction in values of these parameters was interpreted
as general anxiety. In the social preference test, social preference ratio was
calculated for each animal, according to the previously published protocol [3],
and reduction in this ratio was interpreted as social anxiety. 2-way ANOVA, with
sex and isolation stress as factors, was used for parametric data analysis, and
Fischer’s post hoc test was used to detect statistically significant between group
differences. Kruskal-Wallis test was used for non-parametric data analysis, and
Mann-Whitney post hoc test with multiple comparison correction was used to
detect statistically significant between group differences.
Results: Compared to control rats, time spent in the centre of open field (-44%
[95%CI: -76%, -12%] p¼0,008) and total distance travelled (-17% [95%CI:
-32%, -2%], p¼0.028) were decreased in isolated males, but not in females
(p>0.1). In elevated plus maze test, time spent in the open arms was significantly
decreased in male isolated rats (isolated: [median: 0.76, IQR: 0.00 – 2.06] vs
control: [median: 4.96, IQR: 2.04 – 17.75], p¼0.034); however, this change did
not remain significant after multiple comparisons corrections. In sociability tests,
both male and female isolated rats exhibited increase in social preference ratio
(+32% [95%CI: 12%, 51%], p¼0.002) and preference for novel animal over
familiar one (+48% [95%CI: 10%, 86%], p¼0.015), compared to control rats.
Body weight, measured after six weeks of social isolation at week ten, was
increased in isolated male compared to control rats (+19% [95%CI: 14%, 24%],
p<0.001), while there was no such difference observed in female rats.
Conclusion: Social isolation caused increase in general anxiety in male, but not
female rats. In addition, both male and female rats exhibited robust increase in
preference for social interaction and novel social stimulus, which is the result
opposite from the expected social anxiety as initially hypothesized.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats",
volume = "1",
number = "Supplement 2",
pages = "19-19",
doi = "10.1016/j.nsa.2022.100149"
}

Manojlović, M., Milosavljević, F., Atanasov, A., Batinić, B., Sitarica, P.,& Jukić, M.. (2022). Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats. in Neuroscience Applied
Elsevier., 1(Supplement 2), 19-19.
https://doi.org/10.1016/j.nsa.2022.100149

Manojlović M, Milosavljević F, Atanasov A, Batinić B, Sitarica P, Jukić M. Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats. in Neuroscience Applied. 2022;1(Supplement 2):19-19.
doi:10.1016/j.nsa.2022.100149 .

Manojlović, Marina, Milosavljević, Filip, Atanasov, Andrea, Batinić, Bojan, Sitarica, Pavle, Jukić, Marin, "Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats" in Neuroscience Applied, 1, no. Supplement 2 (2022):19-19,
https://doi.org/10.1016/j.nsa.2022.100149 . .

TY  - CONF
AU  - Milosavljević, Filip
AU  - Brusini, Irene
AU  - Atanasov, Andrea
AU  - Manojlović, Marina
AU  - Vučić, Marija
AU  - Oreščanin-Dušić, Zorana
AU  - Brkljačić, Jelena
AU  - Sitarica, Pavle
AU  - Miljević, Čedo
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Wang, Chunliang
AU  - Damberg, Peter
AU  - Pešić, Vesna
AU  - Tyndale, Rachel
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4729
AB  - Background: Animal models are essential for understanding aetiology and pathophysiology of movement disorders. Previously, it had been found that mice transgenic for the human CYP2C19 gene, which is expressed in the liver and developing brain, exhibit altered neurodevelopment associated with impairments of their motor function and emotionality [1, 2]. The aim of this study was to characterize motoric phenotype of the CYP2C19 transgenic mouse and validate its potential usefulness as an animal model for ataxia.

Methods: Experiments were performed on CYP2C19 transgenic mice and control wild-type littermate mice. Body weight of mice was measured between the 21st and 42nd postnatal day. Mouse gait was analysed with footprint test [3] in young animals at four time points and once in adult mice. The maximal height of hindpaw elevation while walking was measured offline from the video footage of the footprint test. Motoric function was quantified by the rotarod and beam-walking tests. Structural differences in 20 brain regions of wild-type and transgenic mice were investigated with 9.4T gadolinium-enhanced postmortem neuroimaging. Antioxidative enzyme status was determined in the brain tissue in order to assess potential differences in the brain oxidative-antioxidative balance between wild-type and transgenic mice. When multiple brain regions or multiple antioxidant enzyme activities were analysed, p-values were FDR corrected for multiple comparisons.

Results: CYP2C19 transgenic (TG) animals exhibited approximately 5-10% reduced body weight (p=0.015) during 3rd and 4th postnatal week, while after postnatal day 31, the differences in the body weight were no longer statistically significant. The TG animals exhibited approximately two fold higher maximal hindpaw elevation in young (2.1-fold [CI95%: 2.0, 2.2], p<0.0001) and adult mice (1.9-fold [CI95%: 1.8, 2.1], p<0.0001), compared to wild-types. In the 5th postnatal week, all transgenic mice exhibited increase in elevation of both hindpaws, while after this point they gradually started exhibiting unilateral phenotype until almost all (49 of 51) animals became unilaterally affected in the adulthood. Footprint analysis and rotarod test did not detect significant differences (p>0.1) between TG and control mice in any of the analysed parameters, accounting for all examined time points. CYP2C19 transgenic mice exhibited 14% increase in beam crossing time (14%, [95%CI: 6.4, 22], p=0.0014) and 5.6-fold more paw-slips (p<0.0001, n=89) in the beam-walking test. CYP2C19 transgenic mice exhibited profound reduction in cerebellar volume (-11.8% [95%CI: -14.7, -9.0], q<0.0001, n=59) and moderate reduction in hippocampal volume (-4.2% [95%CI: -6.4%, -1.9%], q=0.015, n=59); compared to the corresponding volumes measured in WT mice. Superoxide dismutase activity was slightly increased (1.14-fold [CI95%: 1.06, 1.23], p=0.0010, q=0.023) in the cerebelli and moderately increased (1.3-fold, [CI95%: 1.18, 1.47], p<0.0001, q=0.0013) in the hippocampi of transgenic mice compared to wild-types, while glutathione reductase activity was significantly increased (1.2-fold [CI95%: 1.13, 1.35], p<0.0001, q=0.0021) in the hippocampi of TG mice.

Conclusions: Humanized CYP2C19 transgenic mice exhibit altered motoric function, functional motoric impairments and reduced cerebellar volume. CYP2C19 transgenic mice can be a useful tool for the studies focused on understanding the physiology of cerebellar development, as well as aetiology and pathophysiology of cerebellum-related disorders.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia
VL  - 1
IS  - Supplement 2
SP  - 64
EP  - 64
DO  - 10.1016/j.nsa.2022.100236
ER  - 

@conference{
author = "Milosavljević, Filip and Brusini, Irene and Atanasov, Andrea and Manojlović, Marina and Vučić, Marija and Oreščanin-Dušić, Zorana and Brkljačić, Jelena and Sitarica, Pavle and Miljević, Čedo and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Wang, Chunliang and Damberg, Peter and Pešić, Vesna and Tyndale, Rachel and Ingelman-Sundberg, Magnus and Jukić, Marin",
year = "2022",
abstract = "Background: Animal models are essential for understanding aetiology and pathophysiology of movement disorders. Previously, it had been found that mice transgenic for the human CYP2C19 gene, which is expressed in the liver and developing brain, exhibit altered neurodevelopment associated with impairments of their motor function and emotionality [1, 2]. The aim of this study was to characterize motoric phenotype of the CYP2C19 transgenic mouse and validate its potential usefulness as an animal model for ataxia.

Methods: Experiments were performed on CYP2C19 transgenic mice and control wild-type littermate mice. Body weight of mice was measured between the 21st and 42nd postnatal day. Mouse gait was analysed with footprint test [3] in young animals at four time points and once in adult mice. The maximal height of hindpaw elevation while walking was measured offline from the video footage of the footprint test. Motoric function was quantified by the rotarod and beam-walking tests. Structural differences in 20 brain regions of wild-type and transgenic mice were investigated with 9.4T gadolinium-enhanced postmortem neuroimaging. Antioxidative enzyme status was determined in the brain tissue in order to assess potential differences in the brain oxidative-antioxidative balance between wild-type and transgenic mice. When multiple brain regions or multiple antioxidant enzyme activities were analysed, p-values were FDR corrected for multiple comparisons.

Results: CYP2C19 transgenic (TG) animals exhibited approximately 5-10% reduced body weight (p=0.015) during 3rd and 4th postnatal week, while after postnatal day 31, the differences in the body weight were no longer statistically significant. The TG animals exhibited approximately two fold higher maximal hindpaw elevation in young (2.1-fold [CI95%: 2.0, 2.2], p<0.0001) and adult mice (1.9-fold [CI95%: 1.8, 2.1], p<0.0001), compared to wild-types. In the 5th postnatal week, all transgenic mice exhibited increase in elevation of both hindpaws, while after this point they gradually started exhibiting unilateral phenotype until almost all (49 of 51) animals became unilaterally affected in the adulthood. Footprint analysis and rotarod test did not detect significant differences (p>0.1) between TG and control mice in any of the analysed parameters, accounting for all examined time points. CYP2C19 transgenic mice exhibited 14% increase in beam crossing time (14%, [95%CI: 6.4, 22], p=0.0014) and 5.6-fold more paw-slips (p<0.0001, n=89) in the beam-walking test. CYP2C19 transgenic mice exhibited profound reduction in cerebellar volume (-11.8% [95%CI: -14.7, -9.0], q<0.0001, n=59) and moderate reduction in hippocampal volume (-4.2% [95%CI: -6.4%, -1.9%], q=0.015, n=59); compared to the corresponding volumes measured in WT mice. Superoxide dismutase activity was slightly increased (1.14-fold [CI95%: 1.06, 1.23], p=0.0010, q=0.023) in the cerebelli and moderately increased (1.3-fold, [CI95%: 1.18, 1.47], p<0.0001, q=0.0013) in the hippocampi of transgenic mice compared to wild-types, while glutathione reductase activity was significantly increased (1.2-fold [CI95%: 1.13, 1.35], p<0.0001, q=0.0021) in the hippocampi of TG mice.

Conclusions: Humanized CYP2C19 transgenic mice exhibit altered motoric function, functional motoric impairments and reduced cerebellar volume. CYP2C19 transgenic mice can be a useful tool for the studies focused on understanding the physiology of cerebellar development, as well as aetiology and pathophysiology of cerebellum-related disorders.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia",
volume = "1",
number = "Supplement 2",
pages = "64-64",
doi = "10.1016/j.nsa.2022.100236"
}

Milosavljević, F., Brusini, I., Atanasov, A., Manojlović, M., Vučić, M., Oreščanin-Dušić, Z., Brkljačić, J., Sitarica, P., Miljević, Č., Nikolić-Kokić, A., Blagojević, D., Wang, C., Damberg, P., Pešić, V., Tyndale, R., Ingelman-Sundberg, M.,& Jukić, M.. (2022). Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia. in Neuroscience Applied
Elsevier., 1(Supplement 2), 64-64.
https://doi.org/10.1016/j.nsa.2022.100236

Milosavljević F, Brusini I, Atanasov A, Manojlović M, Vučić M, Oreščanin-Dušić Z, Brkljačić J, Sitarica P, Miljević Č, Nikolić-Kokić A, Blagojević D, Wang C, Damberg P, Pešić V, Tyndale R, Ingelman-Sundberg M, Jukić M. Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia. in Neuroscience Applied. 2022;1(Supplement 2):64-64.
doi:10.1016/j.nsa.2022.100236 .

Milosavljević, Filip, Brusini, Irene, Atanasov, Andrea, Manojlović, Marina, Vučić, Marija, Oreščanin-Dušić, Zorana, Brkljačić, Jelena, Sitarica, Pavle, Miljević, Čedo, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Wang, Chunliang, Damberg, Peter, Pešić, Vesna, Tyndale, Rachel, Ingelman-Sundberg, Magnus, Jukić, Marin, "Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia" in Neuroscience Applied, 1, no. Supplement 2 (2022):64-64,
https://doi.org/10.1016/j.nsa.2022.100236 . .

TY  - CONF
AU  - Atanasov, Andrea
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3832
AB  - Увод: Обзиром да већина психијатријских пацијената примењује више лекова у терапији, аналитичке методе које омогућавају истовремено одређивање концентрације већег броја лекова у истом узорку могу бити корисне за терапијско праћење ових пацијената. Пожељно је да метода буде једноставна и лака за извођење, као и да омогући брзо добијање резултата.
Циљ рада: Валидација хроматографске (HPLC-MS/MS) методе за истовремено одређивање концентрације сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента.
Материјал и методе: Узорци плазме припремљени су методом депротеинизације. Оптимално раздвајање испитиваних лекова постигнуто је на ZORBAX Eclipse XDB-Phenyl колони на температури од 40°C. Мобилна фаза састојала се од ацетонитрила и воденог раствора 0,1% мравље киселине (60:40, v/v). Mасени спектри снимани су у MRM моду коришћењем извора са електроспреј позитивном јонизацијом и тандемске масене детекције. Контролни узорци припремљени су у квинтуликату у три релевантне концентрације за све испитиване лекове. Испитивани су следећи параметри валидације: линеарност, тачност и прецизност.
Резултати: Вредности детерминационих коефицијената (R2) биле су веће од 0,99, док су релативне разлике између номиналних и измерених концентрација (RE) и коефицијенти варијације (CV) били мањи од 15%.
Закључак: Метода течне хроматографије високих перформанси спрегнута са тандем масеним детектором (HPLC-MS/MS) је валидирана у погледу линеарности, тачности и прецизности за истовремено одређивање концентрације сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента. Такође, припрема узорака је брза и једноставна, што је од значаја из практичних разлога.
AB  - Introduction: Since most psychiatric patients use multiple drugs in therapy, analytical methods that allow simultaneous determination of several drugs in the same sample can be useful for therapeutic drug monitoring in these patients. It is also desirable that the method is simple, straightforward and fast.
The Aim: Validation of HPLC-MS/MS method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma.
Material and Methods: Plasma samples were prepared by deproteinization. The optimal separation was achieved by using ZORBAX Eclipse XDB-Phenyl column at the fixed temperature of 40°C. Mobile phase consisted of acetonitrile and 0,1% formic acid in water (60:40, v/v). Drug peaks were detected in the MRM mode by using a positive electrospray source with tandem mass spectrometry detection. Quality control samples were prepared in quintiplicates in three relevant concentrations for each drug. The following validation parameters were examined: linearity, accuracy and precision.
Results: Coefficients of determination (R2) were higher than 0.99, while relative difference between nominal and measured concentrations RE (relative error) and coefficient of variation CV were always lower than 15% .
Conclusion: High performance liquid chromatography coupled with mass detector (HPLC-MS/MS) method was validated with respect to linearity, accuracy and precision for simultaneous determination of sertraline, escitalopram, risperidone and paliperidone in the human plasma. In addition, the sample preparation is relatively fast and straightforward, which is important from the pragmatic reasons.
T1  - Валидација брзе и једноставне хроматографске методе за симултану квантификацију нивоа сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента
T1  - Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3832
ER  - 

@conference{
author = "Atanasov, Andrea",
year = "2021",
abstract = "Увод: Обзиром да већина психијатријских пацијената примењује више лекова у терапији, аналитичке методе које омогућавају истовремено одређивање концентрације већег броја лекова у истом узорку могу бити корисне за терапијско праћење ових пацијената. Пожељно је да метода буде једноставна и лака за извођење, као и да омогући брзо добијање резултата.
Циљ рада: Валидација хроматографске (HPLC-MS/MS) методе за истовремено одређивање концентрације сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента.
Материјал и методе: Узорци плазме припремљени су методом депротеинизације. Оптимално раздвајање испитиваних лекова постигнуто је на ZORBAX Eclipse XDB-Phenyl колони на температури од 40°C. Мобилна фаза састојала се од ацетонитрила и воденог раствора 0,1% мравље киселине (60:40, v/v). Mасени спектри снимани су у MRM моду коришћењем извора са електроспреј позитивном јонизацијом и тандемске масене детекције. Контролни узорци припремљени су у квинтуликату у три релевантне концентрације за све испитиване лекове. Испитивани су следећи параметри валидације: линеарност, тачност и прецизност.
Резултати: Вредности детерминационих коефицијената (R2) биле су веће од 0,99, док су релативне разлике између номиналних и измерених концентрација (RE) и коефицијенти варијације (CV) били мањи од 15%.
Закључак: Метода течне хроматографије високих перформанси спрегнута са тандем масеним детектором (HPLC-MS/MS) је валидирана у погледу линеарности, тачности и прецизности за истовремено одређивање концентрације сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента. Такође, припрема узорака је брза и једноставна, што је од значаја из практичних разлога., Introduction: Since most psychiatric patients use multiple drugs in therapy, analytical methods that allow simultaneous determination of several drugs in the same sample can be useful for therapeutic drug monitoring in these patients. It is also desirable that the method is simple, straightforward and fast.
The Aim: Validation of HPLC-MS/MS method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma.
Material and Methods: Plasma samples were prepared by deproteinization. The optimal separation was achieved by using ZORBAX Eclipse XDB-Phenyl column at the fixed temperature of 40°C. Mobile phase consisted of acetonitrile and 0,1% formic acid in water (60:40, v/v). Drug peaks were detected in the MRM mode by using a positive electrospray source with tandem mass spectrometry detection. Quality control samples were prepared in quintiplicates in three relevant concentrations for each drug. The following validation parameters were examined: linearity, accuracy and precision.
Results: Coefficients of determination (R2) were higher than 0.99, while relative difference between nominal and measured concentrations RE (relative error) and coefficient of variation CV were always lower than 15% .
Conclusion: High performance liquid chromatography coupled with mass detector (HPLC-MS/MS) method was validated with respect to linearity, accuracy and precision for simultaneous determination of sertraline, escitalopram, risperidone and paliperidone in the human plasma. In addition, the sample preparation is relatively fast and straightforward, which is important from the pragmatic reasons.",
title = "Валидација брзе и једноставне хроматографске методе за симултану квантификацију нивоа сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента, Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3832"
}

Atanasov, A.. (2021). Валидација брзе и једноставне хроматографске методе за симултану квантификацију нивоа сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента. .
https://hdl.handle.net/21.15107/rcub_farfar_3832

Atanasov A. Валидација брзе и једноставне хроматографске методе за симултану квантификацију нивоа сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_3832 .

Atanasov, Andrea, "Валидација брзе и једноставне хроматографске методе за симултану квантификацију нивоа сертралина, есциталопрама, рисперидона и палиперидона у плазми пацијента" (2021),
https://hdl.handle.net/21.15107/rcub_farfar_3832 .