Determination of active pharmaceutical ingredient – chloropyramine in dragées

  • Vesna Nace Kostik Quality Manager, Institute of Public Health, Skopje, Macedonia
  • Biljana Gjorgjeska University Goce Delcev, Štip
  • Sofija Petkovska University Goce Delvev, Štip


Chloropyramine is a first generation antihistamine drug approved in some Eastern European countries for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other allergic conditions. Chloropyramine is known as a competitive reversible H1-receptor antagonist. By blocking the effects of histamine, the drug inhibits the vasodilatation, increased vascular permeability, and tissue oedema associated with histamine release in the tissue.

A simple gas chromatography method based on gas chromatography - mass detection technique (GC-MS) for the determination of chloropyramine active pharmaceutical ingredient (API) in dragėes was developed and validated. Chromatographic separation was achieved on a fused silica ZB-5 capillary column (30 m x 0.25 mm i.d. x 0.25 µm film thickness). Acquisition was performed in selected ion monitoring mode (SIM) with target ion (58 m/z) and reference ions (71 m/z, 125 m/z).The method was validated in respect system suitability, specificity, linearity, range accuracy and precision, limit of detection (LOD), limit of quantification (LOQ), specificity, robustness and stability. The advantages of this method include simple sample treatment, short elution time (less than 15 min) and short analysis time (less than 25 min). The proposed method could be applicable for routine analysis in pharmaceutical analytical laboratories.

Keywords: Active pharmaceutical ingredient, chloropyramine, gas chromatography-mass detection, dragėes

Author Biography

Vesna Nace Kostik, Quality Manager, Institute of Public Health, Skopje, Macedonia
Department of contaminanats


J. R Vaughan, G. W. Anderson, R. C. Clapp, J. H Clark, J. P. English, K. L Howard, H. W. Marson, L. H. Sutherland and J. J. Denton, “Antihistamine agents; halogenated N,N-dimethyl-N-benzyl-N-(2-pyridyl)-ethylenediamines”, Journal of Organic Chemistry, vol. 14 (2), pp. 228–234. 1949, doi: 10.1021/jo01154a006.

B.S. Deshmanker, and S. L Agarwal, “The action of three recent antihistaminic drugs ambodryl, sandosten and synopen on bronchial muscle”, Indian J Med Sci., vol. 13, pp. 762-766, 1959, PMID: 13816133M.

E.V. Kurenova, D.L Hunt, D. He, A.T. Magis, D.A. Ostrov, W.G. Cance, “Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo”, J Med Chem., vol. 52(15), pp 4716-24, 2009 Aug 13, doi: 10.1021/jm900159g.

G. Wilhelmi, “The analgesic effects of anti-inflammatory drugs from the point of view of different pharmacological test methods”, Acta Med. Okayama, vol. 18, pp. 297-310, 1964.Matlock, H., and Reese, L.C., 1960, Generalized solutions for laterally loaded piles., Journal of Soil Mechanics and Foundation, 86(5), 63–91.

D. zaghi, H.I. Maibach, “Survey of Safety and efficacy information in drug inserts for topical prescription medications", American Journal of Clinical Dermatology, vol. 8(1), 2007, pp. 43–46,doi:10.2165/00128071-200708010-00006.

S. E Wolverton, “Comprehensive Dermatologic Drug Therapy”, WB Saunders, pp. 563-572, 2001.

J. Iliaszenko, M. Sokolowska, I. Szlaska, and R. Paruszewski, “Gravimetric and spectrophotometric determination of some drugs-tertiary amine hydrochlorides in coated tablets”, Acta Polonia Pharmaceutica – Dug research, vol. 57(2), pp. 93-95, 2000.

J. E. Kountourellis, C. K. Markopoulou, and P. P. Georgakopoulos, “An HPLC Method for the Separation and Simultaneous Determination of Antihistamines, Sympathomimetic Amines and Dextromethorphan in Bulk Drug Material and Dosage Forms”, Analytical Letters, vol. 23(5), pp. 883-891, 1990, doi: 10.1080/00032719008052489.

D. Rudolph and L. Holkup, “HPLC determination and quantification of pheniramine and pyrilamine in over the counter cold medicines”, Concordia College Journal of Analytical Chemistry, vol. 1, pp. 29-33, 2010.

M.C.C. Urban, R.M. Mainardes, and M.P. Daflon, “Development and validation of HPLC method for analysis of dexamethsone acetate in microemulsions”, Brazilian Journal of Pharmaceutical Science, vol. 45(1), pp. 87-92, 2009.

M. R. Siddiqui, Z.A. AlOthman, and N. Rahman, “Analytical techniques in pharmaceutical analysis: A review, Arabian Journal of Chemistry”, 2013,

INTERNATIONAL CONFERENCE ON HARMONIATION (ICH); validation of analytical procedures: Methodology, Q2B (CPMP/ICH/281/95), 2003. Available at: Last access on: 8th. Feb. 2015.

BRITISH PHARMACOPOEIA. London: The Stationery Office, 2, 2001, p.A437-A8.

ICH Q2R1: Validation of Analytical Procedures: Text and Methodology. Proceedings of International Conference on Harmonization of Technical Requirements for the Registration of Drugs for Human Use, Geneva, Switzerland, 1996.

ICH, Guideline on Analytical Method Validation, Proceeding of International Convention on Quality for the Pharmaceutical Industry, Toronto, Canada, 2002.

Center for drug Evaluation and Research, Food and Drug Administration. Reviewer Guidance: Validation of Chromatographic methods. Washington, DC: Department of Health and Human Services; 1994.

V. Kostik, B. Djorgeska, S. Petkovska, “Development and validation of GC-MS method for analysis of chloropyramine hydrochloride in ointments”, IOSR Journal of Pharmacy, 5(5), pp. 55-59, 2015.