CC BY
25PHARMACEUTICS
DETERMINATION OF THE QUALITATIVE COMPOSITION AND QUANTITATIVE CONTENT OF HYDROXYCINNAMIC ACIDS IN THE HERBS OF ANISE (PIMPINELLA ANISUM L.)
Umarov U.,
Postgraduate Student of the Department of Analytical Chemistry, National University of Pharmacy,
Kharkiv, Ukraine (https://orcid.org/0000-0001-8981-5908).
Kolisnyk S.,
Doctor of Pharmacy, Professor of the Department of Analytical Chemistry, National University of Pharmacy, Kharkiv, Ukraine (https://orcid.org/0000-0002-4920-6064).
Fathullaeva M.
Candidate of Chemical Sciences, Associate Professor, Head of the Department of Analytical Chemistry, Tashkent Pharmaceutical Institute, Tashkent, Uzbekistan (https://orcid.org/0000-0002-7138-0501).
Abstract
The qualitative composition and quantitative content of hydroxycinnamic acids in the herbs of Pimpinella anisum were determined. The study of methanol extract by liquid chromatography revealed the presence of six hydroxycinnamic acids. Chlorogenic (1,3389 mg / g) and p-coumaric acid (1,0612 mg / g) are found in the largest quantities. The study of antioxidant activity showed that the level of antioxidant activity of methanol extract from Pimpinella anisum herbs is practically not inferior to ascorbic acid.
Keywords: Pimpinella anisum herbs, hydroxycinnamic acids, thin layer chromatography, liquid chromatography, antioxidant activity.
Introduction
Phenolic compounds as secondary metabolites are synthesized in the cells of all plant organs. Being a large and structurally diverse group, this class of organic compounds is characterized with various chemical, physical and biological properties. Plant phenolic compounds have two forms: simple phenols (phenolic acids, phenolic alcohols) and polyphenols (flavonoids, lignans, stilbens, tannins).
In the molecules of phenolic compounds there are hydroxyl groups connected directly to the aromatic ring. Due to the presence of these functional groups, interaction with other biologically active substances (BAS) is possible [1-5].
Phenolic acids are divided into two main groups: benzoic acids containing seven carbon atoms (C6-C1), and cinnamic acids containing nine carbon atoms (C6-C3). Phenolic acids are found in nature in the form of hydroxybenzoic and hydroxycinnamic acids and can be in free or in bound forms.
Hydroxycinnamic acids (HCAs) - derivatives of the phenylpropanoid structure C6-C3 are the main subgroup of phenolic acids, widely distributed in the plant world. Their content is greater in tea leaves, coffee, red wine, various fruits (especially red), vegetables and whole grains. In nature, hydroxycinnamic acids such as p-coumaric, caffeic, ferulic and synapic acids play an important role. Wide distribution and high concentration provide them with a key role in the biosynthesis of more complex phenolic systems. They are secondary metabolites and are found in several conjugated forms, including amides (conjugated to mono- or polyamines, amino acids or peptides), esters, mainly hydroxy acid esters such as tartaric acid and sugar derivatives, and glycosides.
It should be noted that cinnamic esters in higher plants are present in large quantities, and cinnamic acid amides are rare [6].
p-Coumaric acid is a phenolic acid synthesized mainly from tyrosine and phenylalanine. It is the main precursor in the synthesis of other phenolic acids, such as caffeic, chlorogenic, rosmarinic and ferulic. Distributed in fruits, vegetables, cereals and mushrooms [7-8].
p-Coumaric acid and its conjugated forms have antioxidant, antimicrobial, antitumor, anti-inflammatory, antiplatelet, and other interesting health benefits [9].
Caffeic acid is one of the most common phenolic acids found in fruits, vegetables, mushrooms and herbs. It is biosynthesized by hydroxylation of p-coumaric acid and has an antioxidant, antitumor, anti-inflammatory, antimicrobial and antidiabetic effect [10-11].
Ferulic acid, 4-hydroxy-3-methoxycinnamic acid, is found in drinks (coffee, beer), fruits (cabbage, potatoes, carrots), vegetables (broccoli, spinach, tomatoes), cereals (wheat, corn), flowers and nuts [12-13]. This is a derivative of caffeic acid, formed by the action of the enzyme caffeate O-methyltransferase. It has antioxi-dant, antitumor and anti-inflammatory effects. Currently, much attention is paid to its inclusion in cosmetic emulsions for topical application [14].
Synapic acid, which has antioxidant and anti-inflammatory properties, is present in fruits and vegetables. It is formed as a result of methoxyl and hydroxyl substitution of caffeic acid to form an intermediate fer-ulic acid, which is then methylated to form synapic acid. Methoxyl and hydroxyl groups in the structure of synapic acid have high activity to remove radicals [15].
Plant polyphenols, such as HCAs, have received significant attention from medical researchers due to antioxidant properties [16].
Antioxidants are divided into two groups:
Enzymatic antioxidants are antioxidants that participate directly or indirectly in protecting the body from reactive oxygen species (ROS). These include superoxide dismutase (SOD), catalase, glutathione reductase, etc. [17].
Non-enzymatic antioxidants are antioxidants of food sources that can be divided into several classes. This group includes polyphenols, vitamins, carote-noids, organosulfur compounds and minerals. Among them, polyphenols, namely phenolic acids and flavo-noids, represent the largest class of antioxidants [18].
One of the promising plants that contains this class of biologically active substances is Pimpinella anisum.
Pimpinella anisum is a plant belonging to the family Umbelliferae [19]. Anise, a native of the Eastern Mediterranean region, is grown in many countries around the world.
Anise is mentioned in some sources of Persian medicine, [20], the canon of medicine of Avicenna (980-1037 AD) [21] and the medicine repository written by Aghili Shirazi (1670-1747 AD) [22]. Anis is characterized by such pharmacological effects as anti-fungal, antiviral, antimicrobial, antioxidant, muscle relaxant, anticonvulsant and analgesic. In addition, it has a positive effect in diabetes, hyperlipidemia, dysmenorrhea, and gastrointestinal diseases [23]. In folk medicine, anise is used as an analgesic, sedative, expectorant, carminative, galactogenic and disinfectant [24].
The aim of our study was to study the qualitative composition and quantitative content of hy-droxycinnamic acids in the herbs of Pimpinella anisum, as well as to determine the level of antioxidant activity of the methanol extract of Pimpinella anisum herbs.
Materials and methods. For analysis, we used Pimpinella anisum herbs harvested in the summer of 2019 in Kharkov, Ukraine.
For a preliminary study of the qualitative composition of hydroxycinnamic acids contained in the herbs of Pimpinella anisum, we used thin-layer chromatography, for which an aqueous extract was obtained.
5,0 g of dry raw materials, crushed to a particle size of 2-3 mm, was filled with 25 ml of water (1: 5) and heated under reflux in a boiling water bath for 1 h. The resulting extract was filtered through a pleated filter. Raw materials were extracted twice with new portions of the solvent and the extracts were combined.
For the separation of hydroxycinnamic acids, we selected a mobile system: 15% acetic acid.
Determination by liquid chromatography
Qualitative and quantitative determination of hydroxycinnamic acids was carried out by liquid chroma-tography on an Agilent Technologies 1200.
0,3 g (accurately weighed) of the raw material was extracted into 10 ml of a 60% methanol solution in an ultrasonic bath at 80 ° C for 4 hours in sealed glass vials with a teflon lid. The resulting extract was centrifuged at 3 thousand rpm and filtered through disposable membrane filters with 0,22 pm pores.
Methanol (A) and a 0,1% solution of formic acid in water (B) were used as the mobile phase. Elution was carried out in a gradient mode: 0 min-A (25%): B (75%); 25 min - A (75%): B (25%); 27 min - A (100%): B (0%); 35 min - A (100%): B (0%). Separation was
performed on a Zorbax SB-Aq chromatography column (4,6 mm ± 150 mm, 3,5 pm) (Agilent Technologies, USA), flow rate through the column 0,5 ml / min. Thermostat temperature 30 °C, injection volume 4 pl. Detection was carried out using a diode array detector with signal registration at 250 and 275 nm and fixation of absorption spectra in the range 210-700 nm [25].
For identification and quantitative analysis used standard solutions of hydroxycinnamic acids and ben-zoic acid (aromatic monobasic carboxylic acid).
The content of hydroxycinnamic acids (X) (mg / g) was determined by the formula: X = —,
m
where:
c is the concentration of the compound, determined chromatographically, mg / ml;
V is the volume of extract, ml;
m is the mass of the raw material with which the extraction was carried out, g.
Determination of antioxidant activity
Antioxidant activity was determined using 2,2-di-phenyl-1-picrylhydrazyl (DPPH). 1 ml was taken from 60% methanol extract (E0), diluted to 50 ml in the volumetric flask with the same extractant (dilution E1). 1 ml of E1 was diluted in a volumetric flask with the same extractant to 50 ml (dilution of E2) and so on.
As a standard, ascorbic acid (0,0352 g in 10 ml of the corresponding extractant) was used (A0). 0,5 ml of A0 were taken and 4,5 ml of the same extractant (A1) was added. Selected 0,5 ml of A1 and added 4,5 ml of the same extractant (A2). 0,5 ml of A2 was taken and 4,5 ml of the same extractant (A3) was added.
To prepare the DPPH solution, 10 mg of DPPH (accurately weighed) was placed in a 250,0 ml dark glass volumetric flask, dissolved in 100 ml of distilled methanol, stirred until the sample was dissolved, adjusted the solution volume to the mark with the same solvent and mixed.
An appropriate extractant was used as a comparison solution.
2 ml of solutions were taken: the corresponding extractant was control (K), ascorbic acid (A0 - A3), the studied extract (E0 - E5), 2 ml of a DPPH solution (prepared earlier) was added to each and kept in a dark place for 30 minutes.
The absorption of all solutions was measured on a Shimadzu UV-1800 device (Japan) in quartz cuvettes with an absorbing layer thickness of 10 mm at a wavelength of 517 nm, starting with a comparison solution, then K, A0 - A3 and then E0 - E5 in increasing concentration. Antioxidant activity was calculated by the formula:
AO =
A-A
AK
■ * 100%
AO - antioxidant activity,% Ak - absorption control
Ad is the absorption of the test sample (Ao - A3, Eo
- E5).
Results and its discussion.
As a result of a study of the water extraction of Pimpinella anisum by TLC, it was found that the acid
acid (1,0612 mg / g) are found in the largest quantities. Synapic acid was detected in an amount of 0,2567 mg / g, the content of syringic and trans-ferulic acids is approximately the same and is 0,1026 mg / g and 0,1015 mg / g, respectively. And, finally, the content of trans-cinnamic acid (0,0233 mg / g) was found in the smallest amount. At the same time, gallic, p-hydroxyphenyla-cetic, caffeic and quinic acids were not found in the raw materials.
Table 1
The content of hydroxycinnamic acids in the herbs of anise
No. Substance Void time, min Peak Area, mA * s Content, mg / g
1 Gallic acid 4.81 ND ND
2 p-hydroxyphenylacetic acid 8.33 ND ND
3 Chlorogenic acid 9.99 113.58 1,3389
4 Caffeic acid 10.73 ND ND
5 Syringic acid 12.61 55.02 0,1026
6 Benzoic acid 13.29 133.63 0,2773
7 p-coumaric acid 14.04 516.18 1,0612
8 trans-ferulic acid 14.81 48.9 0,1015
9 Synapic acid 15.72 157.64 0,2567
10 trans-cinnamic acid 17.91 27.67 0,0233
11 Quinic acid 23.01 ND ND
Sum of hydroxycinnamic acids 2,8842 mg/g
Notes: ND - not detected
The content of hydroxycinnamic acids in seeds (Table 2) and in fruits of Pimpinella anisum (table 3) was previously established (Table 3) [27-28]. Three hydroxycinnamic acids were found in seeds grown in North Africa. In this case, rosmarinic acid dominates (1,18 ± 0,03 mg / g - Egypt and 1,38 ± 0,04 - Tunisia, respectively), which we did not find in the Pimpinella anisum herbs. The content of p-coumaric and caffeic acids is several times lower and approximately equal to 0,2 mg / g in the raw materials from Tunisia and 0,05 mg / g in the raw materials from Egypt
Table 2
The content of hydroxycinnamic acids (mg / g) in the seeds of Pimpinella anisum by region of growth
Hydroxycinnamic acids Egypt Tunisia
Caffeic acid 0,05±0,01 0,20±0,02
p-Coumaric acid 0,04±0,01 0,21±0,03
Ferulic acid - -
Chlorogenic acid - -
Neochlorogenic acid - -
Caffeoylquinic acid - -
Feruloylquinic acid - -
3,5-dicaffeoylquinic acid - -
Dicaffeoylquinic acid - -
Rosmarinic acid 1,18±0,03 1,38±0,04
Cinnamic acid - -
Syringic acid - -
Sum of hydroxycinnamic acids 1,27 1,79
spots had blue fluorescence in UV light. After treatment with ammonia vapors, blue fluorescence was enhanced. In comparison with the values of Rf given in the literature [26], ferulic, chlorogenic, and p-coumaric acids were identified.
In the study of the methanol extract of the Pimpi-nella anisum herbs by liquid chromatography, the presence of six hydroxycinnamic acids was established (Table 1). Chlorogenic (1,3389 mg / g) and p-coumaric
Table 3
The content of hydroxycinnamic acids (mg / g) in the fruits of Pimpinella anisum by region of growth
Hydroxycinnamic acids Turkey Spain Greece Malta Syria The island of Crete Italy
Caffeic acid - - - - - - -
p-Coumaric acid - - - - - - -
Ferulic acid 0,0870,108 0,0710,085 - - 0,0380,096 0,039 0,074
Chlorogenic acid 0,0350,076 0,0250,050 0,039 0,112 0,084 - 0,0100,058
Neochlorogenic acid 0,1780,344 0,0960,247 0,211 0,572 0,0550,337 0,055 0,0480,311
Caffeoylquinic acid - - - - - - -
Feruloylquinic acid - - - - - - -
3,5-dicaffeoylquinic acid 0,2010,207 0,1260,178 - 0,514 0,0480,302 0,042 0,1150,234
Rosmarinic acid - - - - - - -
Cinnamic acid - - - - - - -
Syringic acid - - - - - - -
Sum of hydroxycinnamic acids 0,735 0,560 0,25 1,198 0,819 0,136 0,677
The presence of four hydroxycinnamic acids - fer-ulic, 3,5-dicaffeoylquinic, chlorogenic and neochloro-genic - was found in the fruits of Pimpinella anisum grown in seven different regions. The dominant is neo-chlorogenic acid, which was also not found by us in the herbs.
Regarding the content of the amount of hydroxycinnamic acids in the herbs of Pimpinella anisum (2,8842 mg / g), it should be noted that it is on average 2,27 times higher than the content of those in seeds grown in Egypt (1,27 mg / g) and 1,61 times in Tunisia
Antioxidant activity
(1,79 mg / g) and, accordingly, exceeds the content of hydroxycinnamic acids in fruits - from 2,41 (Malta -1,198 mg / g) to 21,21 times (Crete Island - 0,136 mg / g).
In 2011, Turkish researchers studied the antioxidant activity of Pimpinella anisum with DPPH. For this purpose, methanol extract (10 g of plant powder: 100 ml of methanol), infusion (5 g of plant powder: 100 ml of boiled water) and a decoction (10 g of cut into small pieces of plant: 100 ml of boiled water) were obtained [29]. The determination results are shown in table 4.
Table 4
Plant Antioxidant activity, %
Methanol extract Infusion Decoction
Pimpinella anisum 36,4 54,69 55,2
As can be seen from table 4, the nature of the ex-tractant significantly affects the antioxidant activity and with a decrease in the concentration of methanol, the antioxidant activity of the extract increases.
In this regard, interest arose in the study of the an-tioxidant activity of hydroxycinnamic acids isolated from Pimpinella anisum herbs. As a result of our experiment, it was found that in terms of antioxidant activity, the methanol extract from Pimpinella anisum herbs (91,68%) is practically not inferior to ascorbic acid (93,99%).
At the same time, 60% methanol extract obtained by us is 2,5 times more active in terms of antioxidant activity than absolute methanol extract and 1,66 times more active than in infusion and decoction.
Conclusions.
The qualitative composition was studied by the method of liquid chromatography and the quantitative content of hydroxycinnamic acids was determined in the herbs of Pimpinella anisum. The presence of six hydroxycinnamic acids was found, the dominant of which are chlorogenic and p-coumaric acids. It was established that in terms of antioxidant activity, the methanol extract of Pimpinella anisum herbs is practically not inferior to ascorbic acid.
REFERENCES:
1. Rico, M., González, A. G., Santana-Casiano, M., González-Dávila, M., Pérez-Almeida, N., & de Tangil, M. S. (2017). Production of Primary and Secondary Metabolites Using Algae. Prospects and Challenges in Algal Biotechnology, 311— 326. doi:10.1007/978-981-10-1950-0_12.
2. Tsao, R. (2010). Chemistry and Biochemistry of Dietary Polyphenols. Nutrients, 2(12), 12311246. doi:10.3390/nu2121231.
3. Jakobek, L. (2015). Interactions of polyphenols with carbohydrates, lipids and proteins. Food Chemistry, 175, 556-567. doi:10.1016/j.food-chem.2014.12.013.
4. Zhang, H., & Tsao, R. (2016). Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Current Opinion in Food Science, 8, 33-42. doi:10.1016/j.cofs.2016.02.002.
5. Tufarelli, V., Casalino, E., D'Alessandro, A.G., Laudadio, V. (2017). Dietary phenolic compounds: biochemistry, metabolism and significance in animal and human health, Curr. Drug Metab., 18 (10), 905-913. doi:10.2174/1389200218666170925124004.
6. Teixeira, J., Gaspar, A., Garrido, E. M., Garrido, J., & Borges, F. (2013). Hydroxycinnamic Acid Antioxidants: An Electrochemical Overview. BioMed Research International,1-11.doi:10.1155/2013/251754.
7. Jiang, K., Li, L., Long, L., & Ding, S. (2016). Comparison of alkali treatments for efficient release of p-coumaric acid and enzymatic saccharifica-tion of sorghum pith. Bioresource Technology, 207, 110. doi:10.1016/j.biortech.2016.01.116.
8. Pragasam, S. J., Murunikkara, V., Sabina, E. P., & Rasool, M. (2012). Ameliorative effect of p-cou-maric acid, a common dietary phenol, on adjuvant-induced arthritis in rats. Rheumatology International, 33(2), 325-334. doi: 10.1007/s00296-012-2394-4.
9. Pei, K., Ou, J., Huang, J., & Ou, S. (2016). p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. Journal of the Science of Food and Agriculture, 96(9), 2952-2962. doi:10.1002/jsfa.7578.
10. Heleno, S. A., Martins, A., Queiroz, M. J. R. P., & Ferreira, I. C. F. R. (2015). Bioactivity of phenolic acids: Metabolites versus parent compounds: A review. Food Chemistry, 173, 501513. doi:10.1016/j.foodchem.2014.10.057.
11. Yang, W. S., Jeong, D., Yi, Y.-S., Park, J. G., Seo, H., Moh, S. H., ... Cho, J. Y. (2013). IRAK1/4-Targeted Anti-Inflammatory Action of Caffeic Acid. Mediators of Inflammation, 112. doi:10.1155/2013/518183
12. Bhanja Dey, T., Chakraborty, S., Jain, K. K., Sharma, A., & Kuhad, R. C. (2016). Antioxidant phe-nolics and their microbial production by submerged and solid state fermentation process: A review. Trends in Food Science & Technology, 53, 6074. doi:10.1016/j.tifs.2016.04.007.
13. Kumar, N., & Pruthi, V. (2014). Potential applications of ferulic acid from natural sources. Biotechnology Reports, 4, 8693. doi:10.1016/j.btre.2014.09.002.
14. Ouimet, M. A., Faig, J. J., Yu, W., & UhrichT K. E. (2015). Ferulic Acid-Based Polymers with Glycol Functionality as a Versatile Platform for Topical Applications. Biomacromolecules, 16(9), 29112919. doi: 10.1021/acs.biomac.5b00824.
15. Silambarasan, T., Manivannan, J., Raja, B., & Chatterjee, S. (2016). Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid—Role of HMG-CoA reductase. European Journal of Pharmacology, 777, 113-123. doi:10.1016/j.ejphar.2016.03.004.
16. Saranya, B., Sufikarali, T., Chindhu, S., Muneeb, A. M., Leela, N. K., & Zachariah, T. J. (2017). Turmeric and cinnamon dominate in antioxidant potential among four major spices. Journal of Spices and Aromatic Crops, 26(1), 27-32, doi: 10.25081/josac.2017.v26.i1.803
17. Mehta, S. K., & Gowder, S. J. T. (2015). Members of Antioxidant Machinery and Their Functions. Basic Principles and Clinical Significance of Oxidative Stress. doi:10.5772/61884
18. Bunaciu, A. A., Danet, A. F., Fleschin, §., & Aboul-Enein, H. Y. (2015). Recent Applications for in Vitro Antioxidant Activity Assay. Critical Reviews in Analytical Chemistry, 46(5), 389399. doi:10.1080/10408347.2015.1101369.
19. Saini, N., Singh, G.K., Nagor, B.P. (2014). Spasmolytic potential of some medicinal plants belonging to family umbelliferae: A Review. Int. J. Res. Ayurveda Pharm. 5(1):74-83. doi: 10.7897/22774343.05116
20. Hashempur, M. H., Khademi, F., Rahmani-fard, M., & Zarshenas, M. M. (2017). An Evidence-Based Study on Medicinal Plants for Hemorrhoids in Medieval Persia. Journal of Evidence-Based Complementary & Alternative Medicine, 22(4), 969981. doi:10.1177/2156587216688597
21. Mosavat, S. H., Marzban, M., Bahrami, M., Parvizi, M. M., & Hajimonfarednejad, M. (2016). Sexual headache from view point of Avicenna and traditional Persian medicine. Neurological Sciences, 38(1), 193-196. doi:10.1007/s10072-016-2741-4
22. Shakeri, A., Hashempur, M. H., Mojibian, M., Aliasl, F., Bioos, S., & Nejatbakhsh, F. (2018). A comparative study of ranitidine and quince (Cydonia oblonga mill) sauce on gastroesophageal reflux disease (GERD) in pregnancy: a randomised, open-label, active-controlled clinical trial. Journal of Obstetrics and Gynaecology, 17. doi:10.1080/01443615.2018.1431210
23. Shojaii, A., & Abdollahi Fard, M. (2012). Review of Pharmacological Properties and Chemical Constituents of Pimpinella anisum. ISRN Pharmaceutics, 2012, 1-8. doi: 10.5402/2012/510795
24. Aiswarya, N., Chandran, V., Teerthanath, S., Rakesh, K. (2018). Nephroprotective effect of aqueous extract of Pimpinella anisum in gentamicin induced nephrotoxicity in wistar rats. Phcog. J., 10 (3), 403-407. doi:10.5530/pj.2018.3.66
25. Sumere B. R. et al. Combining pressurized liquids with ultrasound to improve the extraction of phe-
nolic compounds from pomegranate peel (Punica gran-atum L.) //Ultrasonics sonochemistry. - 2018. - T. 48.
- C. 151-162.
26. Derzhavna farmakopeya Ukrayini / Derzhavne pIdpriemstvo, «Naukovo - ekspertniy farmakologlchniy tsentr». - 1-e vid. - Dopovnennya 2.
- HarkIv: Derzhavne pIdpriemstvo, «Naukovo - ekspertniy farmakologlchniy tsentr», 2008. - 620s.
27. Bettaieb Rebey, I., Bourgou, S., Aidi Wannes, W., Hamrouni Selami, I., Saidani Tounsi, M., Marzouk, B., ... Ksouri, R. (2017). Comparative assessment of phytochemical profiles and antioxidant properties of Tunisian and Egyptian anise (Pimpinella anisum L.) seeds. Plant Biosystems - An International Journal
Dealing with All Aspects of Plant Biology, 152(5), 971-978. doi:10.1080/11263504.2017.1403394.
28. Iannarelli, R., Caprioli, G., Sut, S., Dall'Ac-qua, S., Fiorini, D., Vittori, S., & Maggi, F. (2017). Valorizing overlooked local crops in the era of globalization: the case of aniseed ( Pimpinella anisum L.) from Castignano (central Italy). Industrial Crops and Products, 104, 99-110. doi:10.1016/j.indcrop.2017.04.028.
29. ALBAYRAK, S., AKSOY, A., SAGDIC, O., & ALBAYRAK, S.(2011). ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF DIFFERENT EXTRACTS OF SOME MEDICINAL HERBS CONSUMED AS TEA AND SPICES IN TURKEY. Journal of Food Biochemistry, 36(5), 547554. doi:10.1111/j.1745-4514.2011.00568.x.
USING RAPFIS SOFTWARE FOR PRODUCTION OF THE RADIOPHARMACEUTICAL "FLUORODEOXYGLUCOSE 18F, SOLUTION FOR INJECTIONS"
Kachaniuk V.
post-graduate student of the Department of Military Pharmacy of the Ukrainian Military Medical Academy, Kyiv, Ukraine
Abstract
To produce high-quality radiopharmaceutical "Fluorodeoxyglucose 18F, solution for injections" (FDG), produced at aseptic conditions and used for diagnostics of oncological diseases by means of positron emission tomography (PET).
FDG is a short-lived radiopharmaceutical with half-life period of 109.8 min, used at nuclear medicine for early diagnostics, dynamics monitoring for surgical and chemotherapy treatment of fast-growing malignancies, characterized with glucose hypermetabolism [1].
For continuous FDG production with ensured quality, it is important to organize the production process with timely and effective indication, tracking and elimination of deviations and failures within the technological process, production and laboratory equipment, as well as technical systems during their use.
Thus, the Radiopharmaceutical Production Failure Indication System (RAPFIS) computer program was developed, with defined perspectives of it's application on the local level at PET-centers producing radiopharmaceu-ticals.
Keywords: radiopharmaceutical, Fluorodeoxyglucose, computer program, software.
FDG production is conducted at aseptic conditions and applied before receiving all the results of laboratory research as its useful life comprises 12 hours since the production date and time [2]. This factor in particular requires creation of effective quality assurance system at all the stages of FDG production. That is why, there is a need to create RAPFIS software, which enables optimization of processes control, such as: issuing variable personnel tasks, preparation for FDG production, tracking deviations in technological process, failures of technological and laboratory equipment, and ensuring corrective and preventive measures - maintenance and scheduled preventive repair of the equipment, replacement of spare parts and planning of supply purchasing, calculation of equipment downtime, financial costs for repair work, planning and timely implementation of preventive actions, collection and statistical processing of information on deviations in the technological process, failure of equipment used for the production and quality control of radiopharmaceuticals. Analysis and assessment of deviations are the input data for effective quality risk management.
RAPFIS software is a closed-cycle system for registration of deviations, their analysis with further development of corrective actions; it is used to increase reliability and sustainability of the technological process, provision of medical diagnostics for the patients with malignancies through PET research.
"Closed cycle" in RAPFIS software means system approach to processing every registered case eliminating the possibility that every failure or flaw remains unnoticed by the members of FDG production technology process.
Program processes of RAPFIS system provide additional benefits of integrated analytical possibilities such as: tracking main indicators of reproducibility of the technological process, control over equipment failure rate, calculation of average time between failures, average time spent for repair works, availability, cost of maintenance and spare parts; it also allows conducting certain calculations by the software users.
Integrated functions for reporting and graphics creations enable using the received data to calculate the dynamics of temporal development, severity of failures and other parameters.
RAPFIS process includes the following stages:
