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Darija ObradovićInstitute of Physics Belgrade, University of Belgrade, Pregrevica 118, 11080 Belgrade, Serbia

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Ivana PešićService for the Pharmaceutical Business and Supply, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia

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Marija ČarapićMedicines and Medical Devices Agency of Serbia, Vojvode Stepe 458, 11000 Belgrade, Serbia

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Saša LazovićInstitute of Physics Belgrade, University of Belgrade, Pregrevica 118, 11080 Belgrade, Serbia

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Danica AgbabaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia

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Abstract

The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds.

Abstract

The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds.

Introduction

Scopolamine (hyoscine) is a tropane alkaloid that can be found in many plants of the Solanaceae (nightshade) family. It is a muscarinic receptor antagonist, the parasympatholytic agent possessing central and peripheral actions. In the central nervous system (CNS), it produces depression of the cerebral cortex, especially of the motor areas, and acts as a powerful hypnotic. When administered prior to general anesthesia, scopolamine calms the patient, reduces secretions, produces amnesia, diminishes some of the side effects of the anesthetic and assists in the induction process. Beside the scopolamine, atropine, homatropine, and noratropine belong to the group of parasympatholytic agents [1–4]. Atropine is used in a treatment of certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate and to decrease saliva production during surgery. Clinical application of homatropine includes its use in eye drops as a cycloplegic (to temporarily paralyze accommodation), and as a mydriatic (to dilate the pupil) [5, 6].

Scopolamine and atropine have similar effects on the peripheral nervous system. However, scopolamine has greater effects on the central nervous system (CNS) than atropine, due to its ability to cross the blood–brain barrier [7]. After atropine application, as a consequence of metabolic transformations, the homatropine and noratropine can be detected. Metabolic demethylation of scopolamine produces norhyoscine.

Several separation methods have been developed for determination of tropane alkaloids in pharmaceutical dosage forms or biological fluids [8–17]. Previous investigations included the application of micellar electrokinetic chromatography in pharmaceutical analysis of tropane alkaloids [15–17]. More recent literature has revealed that the reversed-phase liquid chromatography methods were mostly applied for the separation and determination of scopolamine and atropine [8–11]. Thin layer chromatography (TLC) was successfully applied for their qualitative and quantitative analysis [12–14]. The newest edition of European Pharmacopoeia (EP) [18] and the United States Pharmacopoeia (USP) [19] report on the purity test of structurally similar active pharmaceutical substances (API), hyoscine hydrobromide, atropine sulphate and homatropine hydrobromide by means of the ion-pair or micellar high-performance liquid chromatography (HPLC) using octylsilyl silica gel or the polar end-capped octadecylsilica gel as stationary phases and mobile phase consisting of the mixture of water solution of phosphate buffer, sodium dodecyl sulphate, or sodium heptanesulfonate and acetonitrile [15].

None of the above-described methods has reported on the separation of scopolamine in the presence of related compounds such, as norhyoscine (EP: Impurity B), atropine, noratropine (EP: atropine Impurity B), and homatropine, without using micellar agents in mobile phase. We intended to establish optimal chromatographic conditions for the separation of scopolamine, norhyoscine (EP: Impurity B), atropine, noratropine (EP: atropine Impurity B), and homatropine in the pharmaceutical dosage forms and to this effect, we developed a validated analytical procedure for determination and purity control of scopolamine in the eye drops formulation.

This paper presents the development of chromatographic conditions for the separation of scopolamine and its related compounds, followed by method validation for determination of scopolamine in the eye drops.

Experimental

Chemicals

Reference standards of scopolamine hydrobromide (1R,2R,4S,5S,7s)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4] non-7-yl (2S)-3-hydroxy-2-phenylpropanoate, norhyoscine (1R,2R,4S,5S,7s)-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (2S)-3-hydroxy-2-phenylpropanoate (norhyoscine), atropine sulfate bis[(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate] sulfate monohydrate, and noratropine (1R,3r,5S)-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate were provided by the European Directorate for the Quality of Medicine and Health Care Council of Europe (EDQM, Strasbourg, France). Homatroprine hydrobromide (1R,3R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-2-hydroxy-2-phenylacetate hydrobromide were provided by Hemofarm (Vršac, Serbia) (Fig. 1). Acetonitrile (HPLC grade; Merck, Darmstadt, Germany), methanol (HPLC grade; Sigma-Aldrich, Steinhem, Germany), water (HPLC grade; purified by the Simplicity 185 system, Milipore, Billerica, MA), ammonium-acetate (Merck, Germany), triethylamine (TEA, Fischer Chemical, UK), acetic acid (Fisher Chemicals, UK) were used for preparation of the mobile phase and the solutions.

Fig. 1.
Fig. 1.

Chemical structures of scopolamine and its related compounds

Citation: Acta Chromatographica 2023; 10.1556/1326.2022.01107

Eye drops, Scopolamini hydrobromidum 0.25%, were obtained by the Galenic production laboratories, Clinical Center of Serbia (Belgrade, Serbia).

Chromatographic conditions

The HPLC analysis was performed using the Agilent Technologies 1200 HPLC system (Santa Clara, CA, USA) consisting of the binary pump, the degasser, the thermostat for the column, the photodiode array detector and the Zorbax Rx-SIL analytical column (250 × 4.6 mm i.d., 5 μm silica particles size) manufactured by Agilent Technologies (USA). Samples were injected through the Rheodyne injector valve with a 20 μL sample loop. Mobile phase consisted of acetonitrile and 40 mM ammonium acetate/0.05% TEA adjusted with a low quantity of acetic acid to pH 6.5. The flow rate and temperature were set to 1 mL min−1 and 25 °C, respectively. The UV detection was carried out at 210 nm.

In the process of searching for the optimal chromatographic conditions with all tested compounds, standard solutions were prepared in methanol at the concentration of 1 mg mL−1 and they were subsequently diluted with mobile phase (acetonitrile: 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50, v/v), to obtain final concentration of 0.25 mg mL−1. The 20-μL aliquots of final solution were injected into the column.

Retention time (tR) of each compound was used to calculate the logarithm of the retention factor (logk) value, logk = log((tRt0)/t0), where t0 is the column dead time measured as the time of the first baseline perturbation.

The logk parameter can be interpreted with use of the Soczewiński-Wachtmeister equation and in terms of thermodynamics, it is equivalent to Eq. (1) [20–22].
logk=logk0mφ

If φ represents the volume fraction of acetonitrile in mobile phase, the logk0 is assumed as equal to the logarithm of the retention factor of the analyte chromatographed with use of pure water as an eluent, and m is the slope of Eq. (1).

Lipophilicity characteristics

The hydrophibic parameters (log P, log D) were calculated with use of the Marvin Sketch 6.1.0. [23] and presented in a Table 1.

Table 1.

The calculated molecular descriptors of scopolamine and its related compounds

CompoundLog PLog D
Scopolamine0.890.31
Norhyoscine0.51−1.76
Atropine1.57−1.22
Noratropine1.19−2.05
Homatropine1.59−1.20

Validation of chromatographic conditions for scopolamine hydrobromide determination in eye drops

Stock solutions

Stock solution of scopolamine hydrobromide was prepared by dissolving the working standard substance in methanol, at the concentraction of 1.0009 mg mL−1.

Linearity

Linearity was tested in the range from 50 to 150%. Solutions were prepared by diluting an appropiate amount of the stock solution in mobile phase, up to the final concentrations of scopolamine hydrobromide (0.10 mg mL−1, 0.16 mg mL−1, 0.20 mg mL−1, 0.24 mg mL−1, 0.30 mg mL−1).

Accuracy and precision

Precision of the proposed HPLC method was checked by using six solutions that contained 0.20 mg mL−1 scopolamine hydrobromide.

The accuracy study was performed in a triplicate for each concentration level of scopolamine hydrobromidie 80% (0.16 mg mL−1), 100% (0.20 mg mL−1) and 120% (0.24 mg mL−1). The appropiate concentration levels of scopolamine hydrobromide were prepared by diluting stock solution with a mixture of placebo and mobile phase.

Robustness

Robustness of the method was tested by changing the pH value of mobile phase (pH 6.3–6.7) and the column temperature (20–30°C). Sample solutions were prepared by dissolving an appropriate amount of the working standard in mobile phase, up to the concentration of 0.50 mg mL−1.

Sample solutions

  1. (a)Scopolamine hydrobromide API; the amount of ca. 10.07 mg scopolamine hydrobromide API was accurately weighted and transferred to the 50 mL volumetric flask. Then, the compound was dissolved in mobile phase by using an ultrasonic bath.
  2. (b)Scopolamine hydrobromide eye drops (Scopolamini hydrobromidum 0.25%); the 2.0 mL (2.5 mg mL−1) of sample was transferred to the 25 mL volumetric flask and 23 mL mobile phase was added (to obtain the scopolamine hydrobromide concentration of 0.2 mg mL−1).

Preparation of solutions for the assessment of the limit of detection (LOD) and the limit of quantification (LOQ)

The detection and quantification limits were experimentally obtained based on the signal-to-noise (S/N) approach. Stock solutions were diluted to the lowest concentrations that could be determined experimentally, where S/N = 3 for LOD and S/N = 10 for LOQ.

Results and discussion

Retention behaviour of scopolamine and its related substances was investigated on the silica-based HPLC stationary phase taking into the account different ranges of the φ fractions in mobile phase. The best separation conditions were selected and the method was validated.

Optimization of chromatographic conditions for separation of scopolamine hydrobromide and its related compounds

The retention behaviour of scopolamine and its related compounds was tested on the silica stationary phase using the acetonitrile and aqueous solution of 40 mM ammonium acetate as mobile phase. In order to achieve separation of all the compounds and a good peak performance, the 0.5% TEA was added, as well as the low quantity of acetic acid to pH 6.5 mobile phase. It was noticed that the volume fractions of acetonitrile (φ) above 0.60 resulted in a poor peak performanace. Further, the chromatographic conditions within the φ range of 0.400 to 0.550 where appropriate peak shape and separation mechanism can be expected were investigated (Table 2).

Table 2.

The average retention time (tR) for three repeated measurements according to the volume fraction of acetonitrile in mobile phase. The standard deviation values are given in parentheses

φ(ACN)NorhyoscineScopolamineNoratropineAtropineHomatropine
0.4004.73 (0.002)6.05 (0.008)6.44 (0.014)9.02 (0.024)9.49 (0.009)
0.4254.66 (0.008)5.96 (0.006)6.53 (0.003)9.10 (0.008)9.63 (0.006)
0.4504.55 (0.007)5.84 (0.008)6.68 (0.008)9.05 (0.005)9.62 (0.010)
0.5004.50 (0.022)5.72 (0.020)6.59 (0.003)9.07 (0.007)9.64 (0.011)
0.5504.41 (0.008)5.59 (0.008)6.84 (0.008)9.20 (0.008)9.70 (0.008)

Finally, we decided for the mobile phase containing acetonitrile and 40 mM ammonium acetate/0.05% TEA (50:50; v/v), with a low quantity of acetic acid adjusted to pH 6.5, t = 25 °C; λ = 210 nm (Fig. 2).

Fig. 2.
Fig. 2.

The chromatogram of scopolamine and its related compounds. Stationary phase: Zorbax Rx-SIL (250 × 4.6 mm i.d., 5 μm silica particles size); mobile phase: acetonitrile, and 40 mM ammonium acetate/0.05% TEA adjusted with a low quantity of acetic acid to pH 6.5; t = 25°C; λ = 210 nm

Citation: Acta Chromatographica 2023; 10.1556/1326.2022.01107

Upon application of Eq. (1) to the retention data (Table 2), the following mathematical relationships were obtained:

Norhyoscine:
logk=0.0760.680φ,R=0.9566,S.E.=0.0100,p=0.0039
Scopolamine:
logk=0.1380.514φ,R=0.9890,S.E.=0.0038,p=0.0005
Noratropine:
logk=0.117+0.283φ,R=0.7586,S.E.=0.0111,p=0.0545
Atropine:
logk=0.226+0.062φ,R=0.4995,S.E.=0.0043,p=0.1820
Homatropine:
logk=0.259+0.073φ,R=0.6995,S.E.=0.0033,p=0.0775

An increase of the acetonitrile fraction in mobile phase results in an increase of retention with atropine, noratropine and homatropine, while with norhyoscine and scopolamine, the retention decreases. Epoxide derivatives (scopolamine and norhyoscine) with the 50% acetonitrile content in mobile phase demonstrate lower retention. This observation confirms the significance of the reversed-phase interactions which reduce retention of polar compounds in the discussed system. High correlation between the log k value (acetonitrile: 40 mM ammonium acetate/0.05% TEA pH 6.5; 50:50 v/v) and the lipophilicity parameter (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of tropane alkaloids.

After having established optimal chromatographic conditions for the separation of scopolamine hydrobromide and its related compounds (norhyoscine, atropine, noratropine, and homatropine), one has to consider their applicability for fast and efficient determination of scopolamine in pharmaceutical dosage forms. To this effect, we validated the established procedure for determination of scopolamine hydrobromide in the eye drops.

Validation of method for determination of scopolamine hydrobromide in the eye drops

Method selectivity, linearity, precision, accuracy, robustness, limit of quantification (LOQ), and limit of detection (LOD) were determined in the performed validation process [24].

Linearity of the analytical procedure was estimated within the concentration range of 100–300 μg mL−1 of scopolamine hydrobromide. Statistical analysis of the obtained data was performed with use of the linear regression analysis. The results are presented in Table 3 and Fig. 3. As the obtained correlation coefficient (r) was equal to 0.9990, it can be concluded that the calibration plot was within the acceptance criteria of linearity.

Table 3.

The calibration and validation data

Concentration of standard (%, μg mL−1)Peak area (mAU·s)
50100.901035.75
80161.441608.10
100201.801968.00
120242.162262.20
150302.702869.75

Concentration of standard = 9032.93 ·Peak area + 142.17.

r = 0.9990.

Fig. 3.
Fig. 3.

The representative chromatogram of (a) placebo and (b) sample of the scopolamine hydrobromide eye drops

Citation: Acta Chromatographica 2023; 10.1556/1326.2022.01107

The accuracy was evaluated at each of the three concentration levels (80%, 100%, 120%) in triplicate and it was expressed as the recovery value. The recovery ranged from 99.45% to 101.96% and RSD was 1.30%. Additionally, the obtained results showed no interference of the excipients with the peak of interest, thus the proposed method is suitable for quantitative determination of scopolamine in the eye drops.

Repeatability of the devised method was checked by the replicate sample injections (n = 6) of the six individual preparations of scopolamine hydrobromide (0.20  mg mL−1), RSD = 1.61%. In the precision study, the RSD value for scopolamine was equal to 1.22% (≤2.0%) which confirmed high precision of the proposed method. Robustness was tested for the deliberate variations of the mobile phase pH and the column temperature (Table 4).

Table 4.

The results of the robustness test for the proposed method. The obtained retention time (tR) and resolution (Rs) between scopolamine hydrobromide and norhyoscine according to small variations of the mobile phase pH and column temperature

pH6.306.506.70
t°20 °C25 °C30 °C20 °C25 °C30 °C20 °C25 °C30 °C
Retention time (tR)
Norhyoscine4.614.554.524.644.564.524.594.554.46
Scopolamine hydrobromide5.854.795.685.965.825.755.915.825.68
Noratropine6.456.546.376.696.596.616.856.696.83
Atropine8.788.768.539.319.089.069.529.159.35
Homatropine9.289.258.999.929.659.619.989.719.93
Rs (Norhyoscine/Scopolamine)7.267.517.247.327.857.487.747.777.94

From the data summarized in Table 4, it can be concluded that the proposed analytical method remains basically unaffected by the aforementioned deliberate changes in analytical conditions.

In order to consider possibility to determine under the selected working conditions not only scopolamine hydrobromide, but also its four related compounds, we defined the respective LOD and LOQ values (Table 5). They were experimentally determined based on the signal-to-noise (S/N) approach. The S/N values were determined by comparing measured signals from standard solutions with the known low concentrations of the analytes and those of the blank samples. The LOD and LOQ were defined as the minimum concentration at which the analyte can readily be detected and quantified, respectively. The S/N ratios of 3:1 and 10:1 are generally considered as acceptable for estimation of the LOD and LOQ values.

Table 5.

The LOQ and LOD values for scopolamine and its related compounds (norhyoscine, atropine, noratropine, homatropine)

LOD (μg mL−1)LOQ (μg mL−1)
Homatropine0.0550.110
Noratropine0.0130.025
Atropine0.0330.065
Scopolamine0.0150.030
Norhyoscine0.0060.013

According to EP [18], the minimal Rs value between scopolamine and norhyoscine, as well as between homatropine and norhyoscine is Rs = 1.5, while the minimal Rs = 2.5 is recommended for atropine and norhyoscine. Table 6 shows that the Rs values obtained for the neighbouring compounds under the employed working conditions (Fig. 2) are significantly higher than the minimum values recommended by EP [18]. Thus it can be concluded that the newly elaborated method shows high enough selectivity. It was applied to test the content of scopolamine in Scopolamini hydrobromidum 0.25% (the eye drops). The results demonstrated that the content of scopolamine is 101.05%, RSD = 0.5% which is in agreement with 98–102%.

Table 6.

The resolution factor (Rs) values for the neighbouring pairs of compounds (see Fig. 2)

Norhyoscine-ScopolamineScopolamine-NoratropineNoratropine-AtropineAtropine-Homatropine
Rs8.287.8318.303.12

There is a growing interest in secondary metabolites of plants such as tropane alkaloids. That is why a large number of analytical methods have been published for their determination [25–30]. Most methods are aimed at the individual determination of scopolamine and atropine, but not at the simultaneous analysis of tropane alkaloids and related compounds. In our study, a simple isocratic HPLC method was developed for the simultaneous analysis of scopolamine and its related substances involving the use of a commercially available silica based-stationary phase and a mobile phase that is a mixture of acetonitrile and 40 mM ammonium acetate/0.05% TEA. The selected conditions showed higher sensitivity compared to those given in the literature. For the sake of example, the LOD and LOQ values for noratropine and scopolamine (Table 5) are lower than those given in paper [25]. In the developed HPLC method, LOD (scopolamine) < 0.100 μg mL−1 and LOQ (scopolamine) < 0.300–0.600 μg mL−1 which were found in refs. [27–28]. The obtained LOQ (atropine) < 0.100 μg mL−1, LOQ (scopolamine) < 10 μg mL−1, LOD (atropine), and LOD (scopolamine) < 1 μg mL−1 from the ref. [29]. Compared to more complex mode such as strong cation-exchange two-dimensional liquid chromatography, in our case better sensitivity for scopolamine and hyoscyamine were obtained [30].

Conclusions

The HPLC method presented in this study was developed for the separation of scopolamine and its related compounds. It was validated and found as selective, sensitive, precise, accurate and robust. It was applied to pharmaceutical analysis for determination of scopolamine hydrobromide in the eye drops (Scopolamini hydrobromidum 0.25%).

As there is no reference in the literature concerning separation of scopolamine and its four related compounds (norhyoscine, atropine, noratropine, and homatropine), the elaborated chromatographic conditions could be implemented for qualitative and quantitative analysis of these compounds in different pharmaceuticals.

Conflicts of interest

The last author, Danica Agbaba, is a member of the Editorial Board of the journal. Therefore, the submission was handled by a different member of the editorial board, and she did not take part in the review process in any capacity. The other authors declare no conflict of interest.

Acknowledgements

The authors acknowledge funding provided by the Institute of Physics Belgrade, through the grant by the Ministry of Education, Science, and Technological Development of the Republic of Serbia.

References

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Senior editors

Editor(s)-in-Chief: Kowalska, Teresa

Editor(s)-in-Chief: Sajewicz, Mieczyslaw

Editors(s)

  • Danica Agbaba (University of Belgrade, Belgrade, Serbia)
  • Łukasz Komsta (Medical University of Lublin, Lublin, Poland)
  • Ivana Stanimirova-Daszykowska (University of Silesia, Katowice, Poland)
  • Monika Waksmundzka-Hajnos (Medical University of Lublin, Lublin, Poland)

Editorial Board

  • R. Bhushan (The Indian Institute of Technology, Roorkee, India)
  • J. Bojarski (Jagiellonian University, Kraków, Poland)
  • B. Chankvetadze (State University of Tbilisi, Tbilisi, Georgia)
  • M. Daszykowski (University of Silesia, Katowice, Poland)
  • T.H. Dzido (Medical University of Lublin, Lublin, Poland)
  • A. Felinger (University of Pécs, Pécs, Hungary)
  • K. Glowniak (Medical University of Lublin, Lublin, Poland)
  • B. Glód (Siedlce University of Natural Sciences and Humanities, Siedlce, Poland)
  • A. Gumieniczek (Medical University of Lublin, Lublin, Poland)
  • U. Hubicka (Jagiellonian University, Kraków, Poland)
  • K. Kaczmarski (Rzeszow University of Technology, Rzeszów, Poland)
  • H. Kalász (Semmelweis University, Budapest, Hungary)
  • K. Karljiković Rajić (University of Belgrade, Belgrade, Serbia)
  • I. Klebovich (Semmelweis University, Budapest, Hungary)
  • A. Koch (Private Pharmacy, Hamburg, Germany)
  • P. Kus (Univerity of Silesia, Katowice, Poland)
  • D. Mangelings (Free University of Brussels, Brussels, Belgium)
  • E. Mincsovics (Corvinus University of Budapest, Budapest, Hungary)
  • Á. M. Móricz (Centre for Agricultural Research, Budapest, Hungary)
  • G. Morlock (Giessen University, Giessen, Germany)
  • A. Petruczynik (Medical University of Lublin, Lublin, Poland)
  • R. Skibiński (Medical University of Lublin, Lublin, Poland)
  • B. Spangenberg (Offenburg University of Applied Sciences, Germany)
  • T. Tuzimski (Medical University of Lublin, Lublin, Poland)
  • Y. Vander Heyden (Free University of Brussels, Brussels, Belgium)
  • A. Voelkel (Poznań University of Technology, Poznań, Poland)
  • B. Walczak (University of Silesia, Katowice, Poland)
  • W. Wasiak (Adam Mickiewicz University, Poznań, Poland)
  • I.G. Zenkevich (St. Petersburg State University, St. Petersburg, Russian Federation)

 

KOWALSKA, TERESA
E-mail: kowalska@us.edu.pl

SAJEWICZ, MIECZYSLAW
E-mail:msajewic@us.edu.pl

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Days from
68
acceptance
 
to publication
 
Acceptance
51%
Rate

2019  
Total Cites
WoS
495
Impact Factor 1,418
Impact Factor
without
Journal Self Cites
1,374
5 Year
Impact Factor
0,936
Immediacy
Index
0,460
Citable
Items
50
Total
Articles
50
Total
Reviews
0
Cited
Half-Life
6,2
Citing
Half-Life
8,3
Eigenfactor
Score
0,00048
Article Influence
Score
0,164
% Articles
in
Citable Items
100,00
Normalized
Eigenfactor
0,05895
Average
IF
Percentile
20,349
Scimago
H-index
26
Scimago
Journal Rank
0,255
Scopus
Scite Score
226/167=1,4
Scopus
Scite Score Rank
Chemistry (miscellaneous) 240/398 (Q3)
Scopus
SNIP
0,494
Acceptance
Rate
41%

 

Acta Chromatographica
Publication Model Online only
Gold Open Access
Submission Fee none
Article Processing Charge 400 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

Acta Chromatographica
Language English
Size A4
Year of
Foundation
1988
Volumes
per Year
1
Issues
per Year
4
Founder Institute of Chemistry, University of Silesia
Founder's
Address
PL-40-007 Katowice, Poland, Bankowa 12
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2083-5736 (Online)

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