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Continuous Flow Injection Analysis Method for the Determination of a Drug Diphenhydramine Hydrochloride by Using Phosphomolybdic Acid


  • Muntadhar M. Jabbar Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq.
  • Elham N. Mezaal Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq.



Allergy, Antihistamines, Diphenhydramine hydrochloride, Flow injection analysis, Ion pair complex


The study presented a new method for determining diphenhydramine hydrochloride (DPH) in its pure form and some pharmaceutical preparations, within CFIA technique. The method is simple, fast, sensitive, easy to operate, and of a low cost. It is based on the reaction of DPH with phosphomolybdic acid (PMA), in aqueous media, forming a white, slightly yellowish precipitate. The precipitate formed was studied using an Ayah 6S×1-ST-2D solar cell CFI analyzer, by the reflection of incident light off the surfaces of the deposited particles at (0–180°), expressed as the response measured in (mV) . Some chemical and physical variables were studied to provide optimal conditions for the study. The linear range was 0.07-9  mmol/L and it had a correlation coefficient (r) with a value of (0.9998). The limit of detection (L.O.D.) of the new method was 729.55 ng/sample, calculated by gradually diluting the lower limit of the concentration in the linear range (0.07 mmol/L). The % RSD was less than 0.2% for a concentration of 0.1, 4.0 and 10.0 mmol/L of DPH for n = 8. The method was successfully applied in the determination of DPH in three samples from three different pharmaceutical production companies. Using the standard addition method, the new method was compared with the UV-Vis spectrophotometry method at λmax = 258 nm. Both T-test and F-test. The results of the two tests showed no significant difference at a confidence level (95%).


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British pharmacopoeia,London: The stationery office , 2020: I823.

United State Pharmacopoeia and National Formulary USP41 NF36, 2018; 1: 1327.

Paul R M, Vasanth K P, Vkiran K, Deepak K. Analytical method development and validation for simultaneous estimation of diphenhydramine and naproxen in pharmaceutical dosage forms. J Pharm Negat Results 2022; 13(6): 792-798 .

Sapna S, Kuldeep S, Suvarcha C, Kuldeep K. Volumetric compressibility and viscometric properties of diphenhydramine hydrochloride in aqueous solution of electrolytes: an insight into interactional characteristics. J Mol Liq 2021; 342(2): 1-12.

Sanjay M, Timothy B, Emma F, Mary A H, Silas W S, Mark K. A Case of Massive Diphenhydramine and Naproxen Overdose. J Emerg Med. 2021; 61(3): 259-264.

Noor Al-Huda A R, Khalid Al-Janabi Spectrophotometric determination of diphenhydramine HCL in pure and pharmaceutical formulations using thymol blue. Ann Trop Med Public Health 2021; 24(2): 242-253.

Cesar A S, Renato A S, Cristian A P, David R C, Diego P O, Maria I T. Sensitive kinetic spectrophotometric method for the determination of diphenhydramine in real samples. J Chil Chem Soc. 2019; 64(3): 4507-4512.

Nandeesha I M, Basppa C Y, Manjunatha D H. Liquid chromatographic method development and validation for the simultaneous determination of phenylephrine hydrochloride, paracetamol, caffeine and diphenhydramine hydrochloride in pure and formulations. Research J Pharm Tech 2022; 15(9): 3993-3998.

Hina J, Syed Nisar H S, Nida J. Development and validation of HPLC method for diphenhydramine hydrochloride. RADS J Pharm Pharm Sci. 2020; 8(3): 154-160.

AL-Salman H N K, Erfan A S, Rajaa H F, Hussein H H, Ekhlas Q J. Development of the stable, reliable, fast and simple RP-HPLC analytical method for quantifying diphenhydramine –HCl(DPH) in pharmaceuticals. Int J Pharm Res. 2020; 12(4): 4457-4467.

Revati S, Leena T, Vandana J. Novel rapid isocratic RP-HPLC method for simultaneous estimation of phenylephrine hydrochloride, paracetamol, caffeine, diphenhydramine hydrochloride. Curr Pharm Anal 2021; 17(6): 792-800.

Chunling Y, Yuhai T, Xiaonian H. Flow injection chemiluminescence analysis of diphenhydramine hydrochloride and chlorpheniramine maleate. Instrum Sci Technol 2006; 34: 529-536.

Changzhi Z, Xiaoli C, Shengchen T, Minghua L, Kui J. Selective determination of diphenhydramine in compound pharmaceutical containing ephedrine by flow injection electrochemiluminescence . Anal Sci. 2008; 24: 535-538.

Eman Y Z, Gehad G M, Wael G E. Potentiometric determination of antihistaminic diphenhydramine hydrochloride inpharmaceutical preparations and biological fluids using screen-printed electrode. Bioelectrochemistry 2011; 82(2): 79-86.

Issam M A Shakir, Bashaer A K. A novel online coupling of ion selective electrode with the flow injection system for the determination of vitamin B1. Baghdad Sci J. 2016; 13(2): 458-469.

Jasim M S Jamur, Sumayha M A, Zahra M A. Analytical Methods for Determination of Ketoprofen Drug: A review Ibn Al-Haitham J Pure Appl Sci. 2022; 35(3): 76-82.

Jalal N Jeber, Nagham S Turkey An optoelectronic flow-through detectors for active ingredients determination in the pharmaceutical formulations. J Pharm Biomed Anal 2021; 201: 1-11.

Ghadah F H, Nagham S T. A new continuous flow injection analysis method with NAG-ADF-300-2 Analyzer for promethazine-HCl by cadmium iodide as a precipitating reagent. Chem Methodol. 2021; 5: 498-512.

Sarah F H, Nagham S T. Determination of Ferrous Ion in Pure & Pharmaceutical Preparation by Continuous Flow Injection Analysis Via Turbidmetric Utilizing NAG-4SX3-3D Analyzer. Egypt J Chem. 2022; 65(13): 871 - 886.

Zahraa D, Nagham S T. New Turbidimetric Method for Determination of Cefotaxime Sodium in Pharmaceutical Drugs Using Continuous Flow Injection Manifold Design with CFTS- Vanadium Oxide Sulfate System. Chem Methodol. 2022; 6: 91-102.

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 Sci J. 2020; 17(1): 78-92.

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 J Pure Appl Sci. 2020; 33(1): 65-83.

Zahraa N A, Nagam S T. New turbidimetric method for determination of ciprofloxacin hydrochloride in pharmaceutical drugs using continuous flow injection manifold design with CIP.HCL-sodium nitro prusside system. Eurasian Chem Commun. 2021; 3: 743-754.

Nagam Shakir Turkie, Hussein Fares Abd-Alrazack Newly developed method for determination Indomethacin using Phosphotungstic acid by continue flow injection analysis via homemade ISNAG-fluorimeter. IOSR-J Appl Chem. 2018; 11(2): 25-39.

Hashim J A, Bushra B Q. Development and validation CFIA/MZ system as a green method for determination of thiol drug(D-PEN). Egypt J Chem. 2022; 65(1): 259-270.

Nagham S T, Jalal N J. Flow injection analysis with turbidity detection for the quantitative determination of mebeverine hydrochloride in pharmaceutical formulations. Baghdad Sci J. 2022; 19(1): 141-154.

Nagam S T, 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 Sci J. 2017; 14(4): 773-786.

Read F H. New mode semi-automated turbidimetric determination of mefenamic acid by Ayah 6SX1-ST-2D solar cell-CFI analyser. Res J Pharm Technol 2019; 12(12): 5773-5780.

Miler J C, Miler J N. Statistics for analytical chemistry .6th ed. St. John Wiley and N.Y.Sons 2010, p: 145