221 This work is licensed under a Creative Commons Attribution 4.0 International License IHJPAS. 37 (1) 2024 Ibn Al-Haitham Journal for Pure and Applied Sciences Journal homepage: jih.uobaghdad.edu.iq PISSN: 1609-4042, EISSN: 2521-3407 1, 2 Department of chemistry, college of Education for Pure Sciences Ibn-Al-Haitham, University of Baghdad, Baghdad, Iraq. 3College of Remote Sensing & Geophysics, Al-Karkh University for Science, Baghdad, Iraq. *Corresponding Author: elham.n.m@ihcoedu.uobaghdad.edu.iq Abstract Continuous flow injection analysis (CFIA) is one of the simplest, easiest, and multilateral analytical automation methods in moist chemical analysis. This method depends on changing the physical and chemical properties of a part of the specimen spread out from the specimen injected into the carrier stream. The CFIA technique uses automatic analysis of samples with high efficiency. The CFIA PC compatibility also allows specimens to be treated automatically, reagents to be added, and reaction conditions to be closely monitored. The CFIA is one of the automated chemical analysis methods in which a successive specimen sample is to be estimated and injected into a vector stream from a flowing solution that meets the reagent and mixes at a specific point, the y-junction, before reaching the detector. However, CFIA does not have a separation method because the sample, carrier stream, and reagent all enter the system simultaneously and move together at a specific flow rate to the end of the system. It is also possible to inject a second specimen sample to be estimated before the first sample reaches the detector. For all the reasons mentioned, the CFIA technique analysis is appropriate, fast, and ideal for analyzing different samples. This general technique deals with solutions and is used for various tasks, including pH measurement, conductivity, colorimetry, titration, and enzyme assays. So, it was used in analytical chemistry to estimate many samples, including medicines, because they are essential substances for human life, and everyone widely uses them. Keywords: Continuous flow injection analysis, Flow rate, Carrier stream, Pharmaceutical drugs, Pure and pharmaceutical preparations. 1. Introduction The continuous flow injection analysis (CFIA) fast technique is an easy, simple, and versatile method in chemical analysis. It is considered one of the methods used to automate other methods; it depends on the chemical and physical factors of a scattered specimen region, from the blueness of the specimen inside the carrier stream and revealing [1]. The first to describe FIA in a patent Received 13 January 2023, Received 8 February 2023, Accepted 20 February 2023, Published 20 January 2024 doi.org/10.30526/37.1.3182 A Review Using Continuous Flow Injection Analysis Technique in the Determination of Several Drugs 3Tamara Ahmed Abdel Karim 2Kawther Ahmed Sadiq 1Elham Nghaimesh Mezaal* https://creativecommons.org/licenses/by/4.0/ https://jih.uobaghdad.edu.iq/index.php/j/index#1609-4042 https://jih.uobaghdad.edu.iq/index.php/j/index#2521-3407 mailto:elham.n.m@ihcoedu.uobaghdad.edu.iq https://orcid.org/0009-0009-5781-4850 mailto:dr.tamara1990@gmail.com https://orcid.org/0000-0003-2981-676X mailto:kawther.a.s@ihcoedu.uobaghdad.edu.iq https://orcid.org/0000-0003-4829-790X mailto:elham.n.m@ihcoedu.uobaghdad.edu.iq IHJPAS. 37 (1) 2024 222 they filed in Denmark in 1974 were Ruzicka and Hansen. Since then, the technology has evolved into a discipline, covering 22 studies in addition to more than 20000 research papers that have become the scope of the method from a tool used to automate processes to a means to improve the performance of spectral and electrochemical instruments. The FIA analysis is defined according to Ruzicka and Hansen [2]. The FIA technique depended on consecutive injects for separated liquid specimens inside a movable, no-segmented persistent vector stream. The injected specimen forms a region, which is transferred towards the detector with the next continual reveal of the target analyte. Stewart, another FIA pioneer, knew FIA in 1981 [3] as the consecutive intromission for separated specimen solutions inside an undivided continuous stream together, following the possibility of detecting the analyzed substance. In 1988, Ruzicka and Hansen [4] recalled the nonattendance of air clips. They decided on the definition of a new FIA Data collection for concentration gusto component: a fluid injected from a specific area, scattered inside continuous unsegmented current for transporter [5]. The FIA passed through three generations. The first generation of FIA was in 1970, complemented via sequential flow injection analysis (SFIA) in 1990. As for the second generation, the recently appeared lab-on-valve (LOV) orderliness, also meaning the bead injection (BI), involves a regenerative bean use approach. The third generation has the clear advantages of automated miniaturization and offers new methods and chemical detections; the third generation revolutionized the concept of sample pre-treatment by facilitating online work and linking it with different detection techniques [6,7]. The FIA offers various advantages over manual methods: - The reaction conditions are strictly controlled - High precision, the mechanical performance of the measurements reduces analyzer error - High productivity - Low cost - Low waste generation - Compatibility with the computer - Ease and simplicity - Automatic processing of samples and solution - Consumption of volumes from samples and reagents is low - Its use wide as it can be linked to various devices - In a closed system, the reaction takes place. Thus, the risk of material exposure, contamination, or sample loss is reduced, preserving the safety of analysts by preventing the risk of direct exposure to materials through taking reagents or products of toxic reactions unparalleled in handling any other technology [8]. 2. Design of FIA Figure 1 shows the simplest flow injection analyzer. The analyzer consists of a pump that drives the current carrier through a narrow tube, an injection valve, and a microreactor in which the specimen region gets distracted and reacts with the ingredients of the carrier stream. In the case of the FIA technique, the equilibrium physical (flow homogenization) has never been detected nowadays. Moreover, the chemical equilibrium doesn't need to be obtained at detection [9]. The reaction product is measured while it passes through the detector cell [10, 11]. IHJPAS. 37 (1) 2024 223 Figure 1. The design of the flow injection analysis system 3. Application of continuous flow injection analysis Continuous flow injection analysis, in general, is a simple, easy, and low-cost technology commonly used and readily available in devices such as a peristaltic pump and a low-pressure injection valve. It provides more sampling, low reagent consumption, samples completed in preparation and detection, versatility and high accuracy, and various devices that can be used as detectors. It offers increased sampling, lower reagent consumption, sample automation preparation and detection, better precision, and high versatility since various detectors may be employed. Table 1 shows the use of the CFIA technique for the estimation of some drugs. Table 1. Summarizes the use of CFIA technique to determine some drugs Analyte Type of sample CFIA method Comment Linear range LOD Ref. Paracetamol Drug CFIA-Merging zone Utilizing the merging zone-CFIA technique with a hexagonal flow cell and a homemade photometric- dependent 704 nm LED, a photosilicon minidetectror was also studied. This method was dependent on the oxidation via Fe (III) solution for paracetamol, which leads to the configuration of Fe (II), which reacts together with potassium hexacyanoferrate (III) to configure prussian blue dye, and the estimation of this dye at 704 nm. 0.1-10 mmol/L 2 nmol/L 12 Ciprofloxacin Pharmaceutical preparation CFIA – CL This method is dependent on the indirect chemiluminescence (CL) reaction to improve the quantity of photons emitted during the oxidation of luminol-H2O2-OH- in the presence of ciprofloxacin as a sensitizer for the reaction. 0.01-1 mmol/L 6.01 ng/sample 13 IHJPAS. 37 (1) 2024 224 Methionine Pharmaceutical preparations CFIA – CL This method for estimation of methionine utilizes chemiluminescence for methionine, sodium hydroxide, and liminal for the generation of a chemiluminescence derivative of luminal. 0.6-20 mmol/L 5 µmol/L 14 Folic acid Drugs CFIA- CL Estimation of folic acid via chemiluminescence: CFIA depends on the formation of an adduct molecule of the formed derivative of luminol with folic acid in an alkaline medium. 0.003- 0.45 mM 0.795 mmol/122µL 15 Metformin Pharmaceutical preparation CFIA Depending on the embedded Cu (II) in the bead of gel structure, it can be utilized to configure red– a magenta color complex (λ max= 530 nm) via the direct reaction of the medicine together with the released Cu (II) from the bead of gel in the middle of alkaline. 0.001-1 mmol/L 0.5 µmol/L 16 Ciprofloxacin- HCl Pharmaceutical formulations CFIA – Turbidimetric This method is based on the estimation of ciprofloxacin in pure form and pharmaceutical formulations via coupling continuous flow injection analysis by turbidimetric at 0-180o and scattered light effect at two opposite positions at 0-90o. It is based upon the formation of a yellowish-white precipitate for complex ion pairs via utilizing potassium hexacyanoferrate in the middle of the water. 1-20 mmol/L 0.55 mmol/L 17 Promethazine- HCl Pure and pharmaceutical preparation CFIA – Photometric This method depended on the in situ detection of colored cationic radicals formed by the oxidation of medicine together with sodium persulphate to pinkish-red species and estimated by utilizing an Ayah 3SX3-3D analyzer. 0-7 mmol/L 3.97 μg/sample 18 Metformin hydrochloride Drug CFIA – Micro photometric This method is for the estimation of metformin hydrochloride via the complexation of the medicine with Cu (II). A colored complex was measured at 530 nm. 0-100 mM 662 ng 19 Amiloride Pure and pharmaceutical preparations CFIA - Turbidimetric A yellowish-white precipitate is formed for the amiloride- phosphomolybdic acid ion pair in the middle of the water. Turbidity was measured via the Ayah 6Sx1-ST-1D CFI analyzer by the attenuation of incident light from the surface precipitated particles in 0-180o. 0.005-10 mmol/L 23.14 µg/sample 20 Fe(III) Drug samples CFIA – Turbidimetric This method depends on the complex composition between Fe (III) and 8- hydroxyquinoline in a medium of ammonium acetate for the formation of a deep green precipitate. This complex was estimated utilizing a linear array Ayah 5SXI-T-1D analyzer. 0.1-8 mmol/L 4.8 × 10−9 M/sample 21 IHJPAS. 37 (1) 2024 225 Chlorpromazine- HCl Pure and pharmaceutical preparation CFIA – Turbidimetric This is based on a reaction between Chlorpromazine-HCl and potassium hexacyanoferrate in a medium that is acidic for complex formation of a precipitate colored greenish-yellow. 3-30 mmol/L 0.12 μg/sample 22 Tetracycline- HCl Pure and pharmaceutical formulation CFIA – Turbidimetric This method depends on the complex formation of yellow precipitate for the tetracycline-phosphomolybdic acid as an ion pair complex in an aqueous medium. Turbidity was measured by a linear array Ayah 5SXI-T-1D analyzer at 0-180°. 0.25-25 mmol/L 96.18 pg/sample 23 Metoclopramide hydrochloride Pure and pharmaceutical preparations CFIA This method is dependent on the oxidation of medicine together with Ce (IV) sulfate in a medium from acid to form a red color complex, which is estimated utilizing a homemade Ayah 6SXI-T-2D solar cell. 0.05-16 mmol/L 0.332 μg/sample 24 Cyproheptadine hydrochloride Pharmaceutical preparations CFIA – Turbidimetric The method is dependent on the formation of an ion pair between CPH-HCl and hexacyanoferrate in an aqueous medium to form a yellow precipitate, utilizing the Ayah 6SXI- T-2D solar cell analyzer via the reflection of incident light from surfaces in 0-180°. 0.5-10 mmol/L 280.72 ng/100 μL 25 Vitamin B1 Pure and pharmaceutical Tablets CFIA – Turbidimetric This method depends on the formation of an ion-pair complex between thiamin chloride and ammonium molybdate in the medium from aqueous to form a complex white precipitate. 0.1-2 mmol/L 1.579 μg/sample 26 Mebeverine Pure form or pharmaceutical dosage CFIA-Quenched fluorescence It is dependent on the fluorescence of fluorescein sodium salt and the quenching effect of fluorescence by mebeverine in an aqueous medium. Using a homemade instrument, a fluorometer and CFI analyzer together laser solid state at 405 nm. 0.05-10 mmol/L 114 ng/sample 27 Cefotaxime sodium Pharmaceutical drugs CFIA - Turbidimetric Estimation of cefotaxime sodium in pharmaceutical drugs It is dependent on the formation of a yellowish- white precipitate for the CFTS-K3 [Fe (CN) 6] ion pair in a medium that is aqueous. Turbidity was measured by the Ayah 6SX1-T-1D solar cell CFIA analyzer by the attenuation of incident light at 0-180o. 1-50 mmol/L 63.739 μg/sample 28 Ketotifen fumarate Pure And tablets CFIA - Turbidimetric The method depends on the reaction of Ce (IV) sulfate together with ketotifen fumarate in a salt medium with sodium chloride to form a greenish-blue precipitate as an ion pair complex. Turbidity was measured via the attenuation of incident light at 0-180o. 0.1-50 mmol/L 1.136 μg/sample 29 IHJPAS. 37 (1) 2024 226 Ketotifen fumarate Pure and pharmaceutical Preparation CFIA - Turbidimetric The method was based on the reaction between phosphomolybidic acid and ketotifen fumarate in a medium of sodium chloride to form a yellowish- green precipitate as an ion pair complex. Turbidity was measured at 0-180o. 0.5-50 mmol/L 4.255 μg/sample 30 Mefenamic acid Pure and pharmaceutical Preparation CFIA – Turbidimetric This method depends on the reaction between Ce (IV) sulfates and mefenamic acid in an aqueous medium to form a bluish-green precipitate. Turbidity was measured via the reversal of incident light at 0- 180o. 0.3-7 mmol/L 7.35 μg/sample 31 Mefenamic acid Pure and pharmaceutical preparation CFIA – Turbidimetric Estimation of mefenamic acid in pure form and pharmaceutical preparation by turbidimetric measurement at 0- 180o via the Ayah 6SX1-ST-2D CFIA analyzer. The method depends on phosphomolybidic acid and mefenamic acid reacting with water to make a blue precipitate that is made up of ion pairs. The reflection of incident light at 0-180° served to measure turbidity. 0.3-7 or 0.3-10 mmol/L 4.92 μg/sample 32 Zinc (II) ion Pure and pharmaceutical preparation CFIA – Turbidimetric This method is dependent on the formation of an ion pair complex among folic acid and ammonium molybdate in an aqueous medium to obtain a gray precipitate complex utilizing the Ayah-6SX1-ST-2D solar cell CFI analyzer. 5-16 mmol/L 79.05 μg/sample 33 Ciprofloxacin Pure or pharmaceutical dosage CFIA-Quenched fluorescence This project is dependent on the fluorescence of fluorescein sodium salt, and it’s quenched by ciprofloxacin hydrochloride in an aqueous medium using a fluorometer CFI analyzer together with a laser solid state at 405 nm. 10-100 mmol/L 8.12 μg/sample 34 Folic acid Pure and pharmaceutical formulations CFIA - Turbidimetric This way is dependent on the formation of ion pair complex among folic acid and ammonium molybdate in an aqueous medium to obtain a gray precipitate complex utilizing Ayah-6SX1-ST-2D solar cell CFI analyzer. 0.01-0.6 mmol/L 131.994 ng/μg 35 Ibuprofen Pure form and drugs CFIA – Turbidimetric Estimation for Ibuprofen in pure form and drugs by CFIA. The method is based on the reaction of Ibuprofen with potassium chromate to form a precipitate using a homemade ASNAG fluorometer. 5-30 mmol/L 1.630 μg/sample 36 Vitamin B9 Pure and pharmaceutical formulations CFIA This method depends on the oxidation of vitamin B9 via Ce (IV) sulphate in sulphuric acid medium to form a red colour complex. Utilizing a homemade Ayah 6SXI-T-2D solar cell analyzer. 0.1-5 mmol/L 5.544 μg/sample 37 IHJPAS. 37 (1) 2024 227 Baclofen In pharmaceutical formulation CFIA – Spectrophotometric A spectrophotometric method for the estimation of baclofen in the pharmaceutical formulation was developed by combining a spectrophotometric detector with flow injection analysis. This method is based on the oxidation of Fe (II) to Fe (III) via baclofen, which also forms complexes in an acidic solution measured at 700 nm. 0.05-25 mmol/L 0.01 mmol/L 38 Cefotaxime sodium Pure and pharmaceutical preparation CFIA-Fluorescence The project for estimation of cefotaxime sodium in the form of pure pharmaceutical preparation by fluorescence measurement in ± 90o by 2 × 4 solar cells of a new homemade ISNAG fluorometer. It is dependent on the quenching of fluorescence of calcein. 10-50 mmol/L 501.314 μg/sample 39 Ibuprofen Pure form and drugs CFIA – Turbidimetric This method is based on the reaction between Ibuprofen and sodium nitroprusside to form a precipitate utilizing an ISNAG fluorometer. 0.5-15 mmol/L 33.934 μg/sample 40 Indomethacin Pure form and drugs CFIA – Turbidimetric The determination of indomethacin in its pure form and drugs by CFIA diverged light. This method depends on the reaction of indomethacin with phosphotungstic acid to form a moff- white precipitate using a homemade ISNAG fluorometer. 0.01-5 mmol/L 320.222 ng/sample 41 Indomethacin Pure form and drugs CFIA – Turbidimetric The method depends on the reaction of the indomethacin with potassium hexacyanoferrate to form an off- white precipitate, utilizing the ISNAG- fluorometer. 0.01-5 mmol/L 698.76 ng/sample 42 Ciprofloxacin hydrochloride Pure and pharmaceutical preparation CFIA-Fluorescence Estimation of ciprofloxacin hydrochloride via fluorescence resonance energy transfer from erythrosine B which used a carrier stream. The method was based on using the FIA system of a new homemade ISNAG fluorometer with fluorescence measurement at ± 90o via a 2 × 4 solar cell. 0.01-0.4 mmol/L 1.736 μg/sample 43 Propranolol Pure and pharmaceutical preparations CFIA – Turbidimetric This method relied on a reaction between propranolol and phosphotungstic acid in a medium of water to produce a yellow precipitate. A long-distance chasing photometer (NAG-ADF-300-2) that contains two cells was applied for turbidity measurements. 0.007-13 (cellA) 5-15 (cell B) mmol/L 207.4792 ng/160 μL 1.2449 μg/160 μL 44 Propranolol Pure and pharmaceutical preparations CFIA – Turbidimetric A method was utilized to determine propranolol together with Bi (III) to prove the efficiency of the long- distance chasing photometer (NAG- ADF-300-2) using continuous flow injection. This project is based on a reaction between propranolol and Bi (III) in a medium of water to obtain a yellow precipitate. 0.1-25 (cell A) 1-40 (cell B) mmol/L 51.8698 363.0886 ng/200 μL 45 IHJPAS. 37 (1) 2024 228 Atenolol Pure and pharmaceutical preparations CFIA – Turbidimetric Utilizing the long-distance chasing photometer NAG-ADF-300-2, which contains two cells, for turbidity measurements optimum parameters were studied to increase the sensitivity of the developed method. The method depended on the reaction between atenolol and ammonium molybdate reagent in a medium of distilled water, utilizing the technique CFIA. 0.1-3.5 (cell A) 0.3-3.5 (cell B) mmol/L 133.1680 532.6720 ng/100 μL 46 Atenolol Pure and pharmaceutical preparations CFIA The method depended on the reaction of atenolol with povidone iodine reagent in the medium of distilled water by using a continuous flow injection analysis technique. A long- distance chasing photometer (NAG- ADF-300-2) that contains two cells was applied for measurements. 2-19 (cell A) 5-19 (cell B) mmol/L 146.4848 ng/55 μL 2.6600 μg/200 μL 47 Methyldopa Pure and pharmaceutical formulations CFIA – Turbidimetric This method is dependent on the formation of an ion-pair compound between methyldopa and potassium hexacyanoferrate in an acidic medium to obtain a yellow precipitate complex utilizing the NAG-ADF-300-2 analyzer. 0.05-35 (cell A) 0.05-25 (cell B) mmol/L 1.4292 μg/200 μL 48 Warfarin Pure form and pharmaceutical formulations CFIA – Turbidimetric Formation of a turbid precipitated output yellow colour due to the reaction between warfarin and potassium dichromate. Using a homemade analyzer (NAG Dual and Solo 0-180o) which contained two consecutive detection zones measuring cells 1 and 2 is described. 2.0-16 (cell 1) 0.7-16 (cell 2) mmol/L 0.58 0.55 mmol/L 49 Promethazine- HCl Pure form and pharmaceutical formulations CFIA – Turbidimetric This study is based on the reaction between promethazine-HCl acid and cadmium iodide in the presence of ammonium acetate to form a white precipitate. The attenuation of incident light at 0-180o served as a proxy for turbidity. 0.25-25 (cell A) 0.1-20 (cell B) mmol/L 360.5574 275.5830 μg/sample 50 Promethazine- HCl Pure and pharmaceutical drug tablets CFIA – Turbidimetric This method uses a low-cost analyzer, the NAG-ADF-300-2 homemade instrument. This work depends on the reaction between promethazine-HCl and phosphomolybdic acid in the presence of ammonium chloride to form a brownish-yellowish ion pair complex and precipitate. 0.5-30 mmol/L 2.1659 0.4332 μg/sample 51 Mesalazine In pharmaceutical forms CFIA – Spectrophotometric In this method, using a manifold with three channels, mesalazine was determined by an oxidative coupling reaction with o-coumaric acid after oxidation with sodium periodate in a basic medium. A blue-color complex was formed and measured at 659 nm. 5-150 μg/mL 4.94 μg/mL 52 IHJPAS. 37 (1) 2024 229 Methyldopa Pure and pharmaceutical formulations CFIA A new, simple, sensitive, and fast- developed method was utilized for the estimation of methyldopa in pure form and pharmaceutical formulations via CFIA. The idea behind this method is that methyldopa and ammonium ceric (IV) nitrate will combine to form a burgundy color complex in water using an NAG-ADF-300-2 analyzer. 0.05-8.3 (cell A) 0.1-8.5 (cell B) mmol/L 952.8000 ng/200 μL 3.3348 μg/200 μL 53 Cefotaxime sodium Pharmaceutical drugs CFIA – Turbidimetric This method uses a handmade ISNAG-fluorimeter. The reaction between cefotaxime sodium and vanadium oxide sulfate produces a precipitate complex. 0.01-20 mmol/L 0.334 g/sample 54 Chlorpromazine- HCl Pure form and pharmaceutical formulations CFIA – Turbidimetric This method is based on precipitation reactions. Together, the NAG-ADF- 300-2 analyzer was utilized to estimate chlorpromazine-HCl via attenuation of light at two steps: the first step at 110 mm and the second step at 60 mm with a 100 mm separation distance. The chlorpromazine-HCl reaction together mixes two reagents, sodium nitrite and sulfanilic acid, to form a yellowish-white precipitate. 0.5-45 (cell A) 1-43 (cell B) mmol/L 0.9984 49.9239 μg/sample 55 Ciprofloxacin- HCl Pure form and pharmaceuticals CFIA – Turbidimetric This method was based on the interaction between Ciprofloxacin- HCl and ammonium metavanadate as a precipitating agent to form an ion- pair association yellow precipitate in the salt medium. The assessment of Ciprofloxacin-HCl using CFI. 0.0-50 mmol/L 0.221 g/sample 56 Oxymetazoline and Vancomycin hydrochloride Pure and pharmaceutical preparations CFIA – Spectrophotometric The CFI-Spectrophotometric method is used for the determination of oxymetazoline (oxy) and vancomycin hydrochloride (van) in pure and dosage forms. The sulfadimidine using a safe chromogenic reagent via diazotization coupling together oxymetazoline and vancomycin hydrochloride to configure azo dyes was measured at 498 nm for oxymetazoline and 441 nm for vancomycin hydrochloride. 5-200 (oxy) 6-200 (van) μg/mL 2.19 (oxy) 1.79 (van) μg/mL 57 Mebeverine hydrochloride In pharmaceutical formulations CFIA – Turbidimetric This method was developed with a low-cost flow injection method and a specific turbidimetric method for the determination of mebeverine hydrochloride in pharmaceutical formulations by using a homemade NAG Dual and Solo (0-180o) analyzer, which contains two cells, for turbidity measurements. 1.0-6.5 (cell 1) 0.7-6.5 (cell 2) mmol/L 0.28 0.21 mmol/L 58 4. Conclusions Continuous flow injection analysis is one of the most important, simple, low-cost techniques. It is used to analyze different types of drugs, solid, liquid, or capsule-shaped, with a meager detection IHJPAS. 37 (1) 2024 230 limit, high sensitivity, and a wide range of linearity compared to other techniques. In addition, FIA technology can automate other methods, making it possible to measure the sample and determine whether the product of the reaction is a residue or a clear solution. One of the advantages of this technique is that the response occurs within a closed system, so it is considered one of the green chemistry techniques that reduce the risks of exposure to hazardous materials and their inhalation by the analyzer. Acknowledgement The authors thank and appreciate the efforts of Prof.Dr. Issam M. A. Shakir Al-Hashimi, for his creativity in manufacturing flow injection analysis devices, and special thanks to Prof.Dr. Nagam Shaker at the Department of Chemistry, College of Science, University of Baghdad. 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Determination of Methionine via chemiluminescence – continuous flow injection analysis. Kerbala Journal of Pharmaceutical Sciences, 2012, 4, 190- 204. https://iraqjournals.com. 15. Issam, M. A.; Marwa, A. Determination of folic acid by chemiluminescence continuous flow injection analysis. Journal of Kufa for Chemical Science, 2012, 1(5), 58-70. https://www.iasj.net/iasj/article/12544. 16. Shakir, I. M. A.; Al-Awadie, N. S. T. Continuous flow injection analysis for the photometric determination of Metformin drug via the release of copper (II) ion from charged gel bead crystal. Iraqi Journal of Science, 2013, 54(1), 17-26. https://www.iasj.net . 17. Nagam, S. Turkey; Ahmed, F. K. Determination of ciprofloxacin-HCl in pharmaceutical formulations by continuous flow injection analysis via turbidimetric (T180 o) and scattered light effect at two opposite position (2N90 o) using Ayah 4SW-3D-T180-2N90-Solar-CFI analyser. Journal of Kerbala University, 2013, 11(4), 153-169. https://www.iasj.net . 18. Issam, M.A. Shakir; Nagam, S. Turkey. Flow injection analysis for the photometric determination of promethazine-HCl in pure and pharmaceutical preparation via oxidation by persulphate using Ayah 3SX3-3D solar micro photometer. Journal Baghdad for Science, 2013, 10(4), 1190-1202. https://doi:10.21123/bsj.2013.10.4.1190-1202. 19. Issam, M. A. Shakir; Basim, I. Al-abdli; Huda, M. N. Continuous flow injection analysis (CFIA) of metformin hydrochloride using microphotmeter equipped with 530 and 550 nm LED. Journal of Al-Nahrain University, 2013, 16(4), 29-36. https://doi:10.22401/JNUS.16.4.04. 20. Issam, M. A. Shakir. New mode for the on-line determination of Amiloride in pure and pharmaceutical preparation using CFIA via the use of Linear Array from six LED (Snow white ) with one solar cell in a homemade Ayah 6SX1-T-1D Solar CFI Analyser . Iraqi Journal of Science, 2014, 55(4B), 1708-1720. https://www.iasj.net. 21. Issam, M.A. Shakir; Mohammad, K.H. New approach for the turbidimetric determination of iron (III) in drug samples of different origins using homemade Linear Array Ayah 5SX1-T- 1D-CFI analyser. Iraqi Journal of Science, 2014, 55(3A), 852-864. https://ijs.uobaghdad.edu.iq. https://injchemistry.uobabylon.edu.iq/ https://injchemistry.uobabylon.edu.iq/ https://doi:1022401/JNUS.15.4.02. https://iraqjournals.com/ https://iraqjournals.com/ https://www.iasj.net/iasj/article/12544 https://www.iasj.net/ https://www.iasj.net/ https://www.iasj.net/ https://doi:10.21123/bsj.2013.10.4.1190-1202. https://doi:10.22401/JNUS.16.4.04. https://www.iasj.net/ https://www.iasj.net/ https://ijs.uobaghdad.edu.iq/ IHJPAS. 37 (1) 2024 232 22. Issam, M. A. Shakir; Mohammad, K. H. New turbidimetric-continuous flow injection analysis method for the determination of chlorpromazine HCl in pharmaceutical preparation using Linear Array Ayah 5SX1-T-1D-CFI analyser. Iraqi Journal of Science, 2014, 55(2B), 594-605. https://ijs.uobaghdad.edu.iq. 23. Issam, M. A. Shakir; Mohammad, K. H. Novel turbidimetric-continuous flow injection analysis method for the determination of tetracycline HCl in pharmaceutical formulation using homemade Linear Array Ayah 5SX1-T-1D-CFI analyser. International Journal of Research in Pharmacy and Chemistry, 2014, 4(4), 946-957. https://www.researchgate.net. 24. Nagam, S.T. Al-Awadie; Kefah, H. I. New mode for the on-line determination of metoclopramide hydrochloride in pure and pharmaceutical preparations via the use of homemade Ayah 6SX1-T-2D solar cell CFI analyser. Iraq Journal of Science, 2015, 56(2C), 1533-1552. https://ijs.uobaghdad.edu.iq. 25. Nagam, S.T. Al-Awadie; Kefah, H. I. A new approach for the turbidimetric determination of cyproheptadine hydrochloride in pharmaceutical preparations by using homemade Linear Array Ayah 6SX1-T-2D solar cell CFI analyser. Journal of Kerbala University, 2015, 13(3), 61-80. https://www.researchgate.net. 26. Nagam, S.T. Al-Awadie; Rana, A. K. Flow injection turbidimetric determination of vitamin B1 using LEDs as a source of irradiation and two solar cells as an energy transducer. International Journal of Science and Research, 2017, 6(6), 813-825. https://doi:10.21275/ART20174264. 27. Issam, M. A. Shakir; Raed F.H. New approach for determination of mebeverine by quenched fluorescence of analytically interested species using continuous flow injection laser diode fluorometer analyser. International Journal of Research in Pharmacy and Chemistry, 2015, 5(4), 725-735. https://www.ijrpc.com. 28. Nagam, S. T. Al-Awadie; Manhl, H. I. Turbidimetric-flow injection analysis method for the determination of cefotaxime sodium in pharmaceutical drugs using AYAH 6SX1-T-1D CFIA instrument. International Journal of Research in Pharmacy and Chemistry, 2016, 6(4), 891- 909. https://www.ijrpc.com. 29. Nagam, S. T. Al-Awadie; Manhl, H. I. Quantitative determination of Ketotifen fumarate in the pure form and tablets via the use of turbidity by reaction with cerium (IV) sulfate using AYAH 6SX1-T-1D CFIA analyser. International Journal of Research in Pharmacy and Chemistry, 2016, 6(3), 411-431. https://www.ijrpc.com. 30. Nagam, S. T.; Manhl, H. I. Ketotifen Fumarate determination via the new approach of turbidity formed by the reaction with phosphomolybidic using Ayah 6SX1-T-1D CFI Analyser. International Journal of Research in Pharmacy and Chemistry, 2016, 6 (2), 230- 248. https://www.ijrpc.com. 31. Nagam, S. T. Al-Awadie; Mustafa, K. K. Determination of mefenamic acid using Ce (IV) sulfate as an oxidant reagent via the use of the new mode of irradiation (array of six identical LEDS) and detection (twin solar cells) through turbidity measurement by CFIA. International Journal of Research in Pharmacy and Chemistry, 2016, 6 (2), 271-290. https://www.ijrpc.com. 32. Nagam, S.T. Al-Awadie; Mustafa, K.K. Determination of mefenamic acid using a new mode of irradiation (array of six identical LEDs) and detection (twin solar cells) through turbidity measurement by CFIA. Iraq Journal of Science, 2016, 57 (2B), 1052-1070. https://ijs.uobaghdad.edu.iq. https://ijs.uobaghdad.edu.iq/ https://ijs.uobaghdad.edu.iq/ https://www.researchgate.net/ https://www.researchgate.net/ https://ijs.uobaghdad.edu.iq/ https://ijs.uobaghdad.edu.iq/ https://www.researchgate.net/ https://www.researchgate.net/ https://doi:10.21275/ART20174264 https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://www.ijrpc.com/ https://ijs.uobaghdad.edu.iq/ IHJPAS. 37 (1) 2024 233 33. Nagam, S. T. Al-Awadie; Mustafa, K. K. Continuous flow injection turbidimetric for determination of zinc (II) ion by ion pair complex with mefenamic acid using AYAH 6SX1- ST-2D solar cell CFI analyser. International Journal of Research in Pharmacy and Chemistry, 2016, 6(4), 650-665. https://www.ijrpc.com. 34. Issam, M. A. Shakir; Raed, F.H. New approach for determination of ciprofloxacin by quenched fluorescence of analytically interested species using continuous flow injection laser diode fluorometer analyser. Iraqi Journal of Science, 2016, 57(1C), 522-533. https://ijs.uobaghdad.edu.iq. 35. Nagam, S. T. Al-Awadie; Rana, A. K. CFIA-Turbidimetric and photometric determination of vitamin B9 (folic acid) using LEDs as a source of irradiation and two solar cells as an energy transducer. Baghdad Science Journal, 2017, 14(4), 773-786. https:/doi:10.21123/bsj.2017.14.4.0773. 36. Nagam, S.T. Al-Awadie; Hussein, F. A. New mode for long path irradiation and two sided detection for the determination of ibuprofen in pure and pharmaceutical drugs using continuous flow feed via the use of ISNAG fluorimeter instrument. International Journal of Science and Research, 2017, 6(8), 201-216. https://doi:10.21275/ART20175883. 37. Nagam, S.T. Al-Awadie; Rana, A. K. CFIA-Colorimetric assessment and photometric determination of vitamin B9 (folic acid) using LEDs as a source of irradiation and two solar cells as an energy transducer. Journal of Pharmacy and Biological Sciences, 2017, 12(5), 10- 22. https://www.semanticscholar.org. 38. Ghadah, F. H. Flow injection spectrophotometric determination of baclofen in pharmaceutical formulations using Prussian blue reaction. Journal of Al-Nahrain University, 2017, 20(1), 17- 24. https://anjs.edu.iq. 39. Hayder, Q. M.; Nagam, S.T. Al-Awadie. Fluorometric determination of cefotaxime sodium in pharmaceuticals preparation via the quenched of the continuous fluorescence of calcein using a homemade ISNAG- continuous flow injection analyser. International Eurasian Conference on Biological and Chemical Sciences, 2018, 26(27), 259-270. https://www.researchgate.net. 40. Nagam, S.T. Al-Awadie; Hussein, F. A. Continuous flow injection analysis precipitation reaction of ibuprofen with sodium nitro prosside using low pressure mercury lamp tube (UV- light) and detection of diverged scattered lights (visible light) at 2 X 900 using multi solar cells that covers 2 X 100 mm distance of 2 mm path length. Journal of Pharmacy and Biological Sciences, 2018, 13(1), 60-75. https://doi:10.9790/3008-1301016075. 41. Nagam, S.T. Al-Awadie; Hussein, F. A. Newly developed method for determination indomethacin using phosphotungstic acid by continuous flow injection analysis via homemade ISNAG – fluorimeter. Journal of Applied Chemistry, 2018, 11(2), 25-39. https://doi:10.9790/5736-1102012539. 42. Nagam, S.T. Al-Awadie; Hussein, F. A. Newly developed method for determination indomethacin using potassium hexacyanoferrate by using ISNAG – fluorimeter homemade via CFIA. Journal of Global Pharma Technology, 2018, 10(6), 447-460. https://www.researchgate.net. 43. Nagam, S.T. Al-Awadie; Hayder, Q. M. New approach for the determination of ciprofloxacin hydrochloride using fluorescence resonance energy transfer (FRET) and continuous flow injection analysis via ISNAG-fluorimeter. Journal of Pharmaceutical Sciences and Research, 2019, 11(4), 1563-1570. https://www.researchgate.net . https://www.ijrpc.com/ https://www.ijrpc.com/ https://ijs.uobaghdad.edu.iq/ https://ijs.uobaghdad.edu.iq/ https://doi:10.21123/bsj.2017.14.4.0773. https://doi:10.21275/ART20175883 https://www.semanticscholar.org/ https://anjs.edu.iq/ https://www.researchgate.net/ https://doi:10.9790/3008-1301016075. https://doi:10.9790/5736-1102012539. https://www.researchgate.net/ https://www.researchgate.net/ IHJPAS. 37 (1) 2024 234 44. Elham, N. M.; Nagam, S. T. New method for the evaluation of propranolol with phosphotungstic acid via long distance chasing photometer (NAG-ADF-300-2) using continuous flow injection analysis. International Journal of Pharmaceutical Research, 2019, 11(4), 42-57. https://doi:10.31838/ijpr/2019.11.04.008. 45. Nagam, S. T; Elham, N. M. Simple and rapid method for estimate of propranolol with Bi (III) via long-distance chasing photometer (NAG-ADF-300-2) utilization continuous flow injection analysis. International Journal of Drug Delivery Technology, 2019, 9(4), 563-574. https://doi:10.25258/ijddt.9.4.9. 46. Nagam, S. T; Elham, N. M. Assessment of long distance chasing photometer (NAG-ADF-300- 2) by estimating the drug atenolol with ammonium molybdate via continuous flow injection analysis. Baghdad Science Journal, 2020, 17(1), 78-92. https://doi:10.21123/bsj.2020.17.1.0078. 47. Elham, N. M.; Nagam, S. T. Assessment of long distance chasing photometer (NAG-ADF- 300-2) by estimating the drug atenolol with povidone iodine via CFIA. Ibn Al- Haitham Journal for Pure and Applied Science, 2020, 33(1), 65-83. https://doi:10.30526/33.1.2383. 48. Nagam, S. T; Elham, N. M. Continuous flow injection analysis, turbidmetric and photometric determination of methyldopa drugs using a new long distance chasing photometer (NAG-ADF- 300-2). Indian Journal of Forensic Medicine & Toxicology, 2020, 14(4), 1494-1500. https://doi:10.37506/ijfmt.v14i4.11810. 49. Nagham, S.T.; Jalal, N.J. Light scattering detector based on light-emitting diodes-solar cells for a flow analysis of warfarin in pure form and pharmaceutical formulations. Journal of Physics: Conference Series, 2021, 2063(1), 1-14. https://doi:10.1088/1742- 6596/2063/1/012006. 50. Ghadah, F. H.; Nagham, S. T. A new continuous flow injection analysis method coupled with NAG-ADF-300-2 analyzer for promethazine-HCl by cadmium iodide as a precipitating reagent. Chemical Methodologies, 2021, 5(6), 498-512. https://doi:10.22034/chemm.2021.138807. 51. Nagham S. T and Ghadah F. H. Promethazine-HCl determination via CFIA-NAG-ADF-300- 2 instrument using phosphomolybdic acid as a precipitating reagent. Asian Journal of green chemistry, 2021, 5, 387-403. https://civilica.com. 52. Hind, H. Continuous flow injection spectrophotometric determination of mesalazine in pharmaceutical forms. Systematic Reviews in Pharmacy, 2021, 12(2), 202-208. https://www.semanticscholar.org. 53. Nagam, S.T; Elham, N.M. Newly developed method for determination of methyldopa drug using ammonium ceric (IV) nitrate by continuous flow injection analysis via homemade NAG- ADF-300-2 analyser. Annals of Tropical Medicine & Public Health, 2021, 24(4), 528-533. https://doi:10.36295/ASRO.2021.24460. 54. Zahraa, D.; Nagham, S.T. New turbidmetric method for determination of cefotaxime sodium in Pharmaceutical drugs using continuous flow injection manifold design with CFTS- Vanadium oxide sulfate system. Chemical Methodologies, 2022, 6(x), 91-102. https://doi:10.22034/chemm.2022.2.2. 55. Nagham, S.T; Ghadah, F.H. Chlorpromazine-HCl determination via its oxidation with sodium nitrite in sulfanilic acid medium via CFIA technique through long distance chasing photometer NAG-ADF-300-2. Journal of Medicinal and Chemical Sciences, 2022, 5(3), 283-298. https://doi:10.26655/JMCHEMSCI.2022.3.1. https://doi:10.31838/ijpr/2019.11.04.008. file:///C:/Users/Majla/Desktop/مجلد%202024/عدم%20دخول%20سكوبس/كيمياء%202024/.%20https:/doi:10.25258/ijddt.9.4.9 file:///C:/Users/Majla/Desktop/مجلد%202024/عدم%20دخول%20سكوبس/كيمياء%202024/.%20https:/doi:10.25258/ijddt.9.4.9 https://doi:10.21123/bsj.2020.17.1.0078. https://doi:10.30526/33.1.2383. https://doi:10.37506/ijfmt.v14i4.11810. https://doi:10.1088/1742-6596/2063/1/012006. https://doi:10.1088/1742-6596/2063/1/012006. https://doi:10.22034/chemm.2021.138807. https://civilica.com/ https://civilica.com/ https://www.semanticscholar.org/ https://doi:10.36295/ASRO.2021.24460. https://doi:10.22034/chemm.2022.2.2. https://doi:10.26655/JMCHEMSCI.2022.3.1. IHJPAS. 37 (1) 2024 235 56. Nagham, S.T.; Ghufran, K. Ciprofloxacin assessment via the formation of precipitate reaction product with ammonium metavanadate as a reagent using ISNAG-fluorimeter. Eurasian Chemical Communications, 2022, 4, 51-65. https://doi:10.22034/ecc.2022.314811.1260. 57. Bayan, H.; Hind, H. Development of continuous flow injection analysis method for determination of Oxymetazoline and Vancomycin hydrochloride in pharmaceutical preparations. Bull. Chemical Society of Ethiopia, 2022, 36(2), 303-313. https://doi:10.4314/bcse.v36i2.5. 58. Nagham, S.T.; Jalal, N.J. Flow injection analysis with turbidity detection for the quantitative determination of Mebeverine hydrochloride in pharmaceutical formulations. Baghdad Science Journal, 2022, 19(1), 141-154. https://doi:10.21123/bsj.2022.19.1.0141. https://doi:10.22034/ecc.2022.314811.1260. https://doi:10.4314/bcse.v36i2.5. https://doi:10.21123/bsj.2022.19.1.0141