Analysis of Residual Solvents-Impurities by HS-GC-FID: Case of Seven Samples of Ciprofloxacin API

Year 2023, Volume: 43 Issue: 1, 32 - 42, 01.03.2023

Derouicha Matmour

https://doi.org/10.52794/hujpharm.1098619

Abstract

Organic volatile impurities known as residual solvents might appear during the production of active pharmaceutical ingredients (APIs). Analysis of residual solvents in pharmaceutical products is necessary due to the potential risk they provide to human health due to their toxicity and unfavorable side effects, as well as the possibility that they may change the physicochemical properties of the pharmaceutical product.
The goal of this study was to analysis 29 residual solvents-impurities using Head Space Gas Chromatography with Flame Ionization Detector (HS-GC-FID) in seven Ciprofloxacin Hydrochloride API samples that were gathered from seven pharmaceutical companies located in Algeria. A flame-ionization detector and a silica column covered with a 1.8 m layer of phase G43 were both installed in the GC. Helium served as the carrier gas, having a split ratio of 1:5 and a linear velocity of 35 cm/s. The temperature of the column began at 40 °C and increased to 240 °C. The temperature of the injection was 140 °C, while the detector temperature was 250 °C. Twenty-nine organic solvents belong to classes 1 and 2 were analyzed in seven samples of Ciprofloxacin Hydrochloride API whose control is mandatory because of their carcinogenic and intrinsic toxicity. Only five solvents were identified wich are Hexane, Toluene, Acetonitrile, Methanol and Dichloromethane in the different samples. All samples collected satisfied the test of identification, so, the confirmation and the quantification procedures weren’t realized. The HS-GC-FID technique used showed that the identified solvents differ from one sample to another of the same molecule. This showed that manufacturers didn’t often use the same solvents to produce the same API, which justifies that residual organic solvent tests weren’t usually mentioned in the specific monographs.

Keywords

Residual solvents, Solvents-impurties, Ciprofloxacin Hydrochloride, Fluoroquinolone, Antibiotic, HS-GC-FID

References

• [1] Goodfellow K. The Analysis of Residual Solvents in Pharmaceuticals using Headspace GC. Reading Scientific Services 2018 :01-02.
• [2] Nacham O, Ho TD, Anderson JL, Webster GK. Use of ionic liquids as headspace gas chromatography diluents for the analysis of residual solvents in pharmaceuticals. J Pharm Biomed Anal 2017,145:879-886.
• [3] ICH Harmonized Guideline. Impurities: Guideline for Residual Solvents Q3C(R6), International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. 2016: 3-21.
• [4] Mirmoghaddam M, Kaykhaii M, Yahyavi H. Recent developments in the determination of residual solvents in pharmaceutical products by microextraction methods. Anal Methods 2015, 7: 8511-8523.
• [5] B’Hymer C. Residual solvent testing: a review of gas-chromatographic and alternative techniques. Pharm Res 2003, 20(3):337-44.
• [6] Witschi C, Doelker E. Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values 1997, 43(3):215-242.
• [7] Camarasu C, Madichie C, Williams R. Recent progress in the determination of volatile impurities in pharmaceuticals. Trends Analyt Chem 2006, 25(8):768-777.
• [8] Vidal, Ciprofloxacin monograph; 2021. [Available at: https://www.vidal.fr/medicaments/ substances/ciprofloxacine-4070.html. Accessed January 5, 2021].
• [9] WebMD, Ciprofloxacin - Uses, Side Effects, and More; 2021. [Available at: https://www. webmd.com/drugs/2/drug-7748/ciprofloxacin-oral/details. Accessed January 5, 2021].
• [10] Ministry of Health, Population and Hospital Reform, Pharmaceutical Products Directorate, Registration under-direction. Algerian medicines nomenclature; 2014. [Available at: http:// www.sante.gov.dz/images/pharmacy/nationalnomenclatureofpharmaceuticalproduct.Accessed January 8, 2015].
• [11] European Pharmacopoeia, 8th edition. Council of Europe. Ciprofloxacin Hydrochloride Monograph. Related substances. Strasbourg, France 2015:1896-97.
• [12] Synthesis route of Ciprofloxacin Hydrochloride. Batch:CICA4066. Chemo S.A. Lugano Branch. Switzerland.
• [13] Synthesis route of Ciprofloxacin Hydrochloride Monohydrate. Batch: 10271610. Dr Reddy’s Laboratories LTD. India.
• [14] Synthesis procedure of Ciprofloxacin Hydrochloride. Batch: 120801. Pharmaceutical Co. LTD. China.
• [15] Synthesis route of Ciprofloxacin Hydrochloride. Batch: KOFA006. Dr Reddy’s Laboratories LTD. India.
• [16] United States Pharmacopeial Convention. Identification, control and quantification of residual solvents: Water soluble items, Procedures A, B and C. In: United States Pharmacopeia and National Formulary (USP-NF). 38th-33th ed. USA, Deutscher Apotheker Verlag, 2017, p. 171-176.
• [17] European Directorate for Medicines Quality and Health Care. Identification and control of residual solvents. In: European Pharmacopoeia. 8th ed. France, EDQM, 2015, p. 134-38.
• [18] European Directorate for Medicines Quality and Health Care. Limits of residual solvents. In: European Pharmacopoeia. 8th ed. France, EDQM, 2015, p. 635-36.
• [19] RESTEK library of online GC chromatograms. Standard Chromatogram of Class 1_USP Residual Solvent Standard Solution for water-soluble substances. Available on: http://www. restek.fr/images/cgram/gc ph1160.pdf [Accessed 05th June 2017].
• [20] RESTEK library of online GC chromatograms. Standard Chromatogram of Class 2_USP_Mix A Residual Solvent Standard Solution. Available from: http://www.restek. com/images/cgram/ gcph1175. pdf. [Accessed 05th June 2017].
• [21] RESTEK library of online GC chromatograms. Standard Chromatogram of Class 2_USP_ Mix B Residual Solvent Standard Solution. Available from: http://www.restek.com/images/cgram/ gcph00911. pdf. [Accessed 05th June 2017].