A validated GC–MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 70; pp. 64 - 70
• Main Authors: Deconinck, E., Canfyn, M., Sacré, P.-Y., Baudewyns, S., Courselle, P., De Beer, J.O.
• Format: Journal Article Web Resource
• Language: English
• Published: Amsterdam Elsevier B.V 01-11-2012; Elsevier; Elsevier Science
• Subjects: acetone; Analysis; Analytical, structural and metabolic biochemistry; benzene; Biological and medical sciences; Calibration; Capsules; carbon tetrachloride; chloroform; Counterfeit; Counterfeit Drugs - analysis; Drug Contamination; ethanol; ethyl acetate; Fraud; Fundamental and applied biological sciences. Psychology; gas chromatography; Gas Chromatography-Mass Spectrometry - standards; GC-MS; General pharmacology; Headspace; headspace analysis; Human health sciences; isopropyl alcohol; Limit of Detection; mass spectrometry; Medical sciences; Method validation; methylene chloride; Pharmacie, pharmacologie & toxicologie; Pharmacology. Drug treatments; Pharmacy, pharmacology & toxicology; Reference Standards; Reproducibility of Results; Residual solvents; Sciences de la santé humaine; screening; solvents; Solvents - analysis; Tablets; Temperature; Time Factors; toluene; United States; Headspace; GC–MS; Residual solvents; Counterfeit; Method validation; Validation; Capsule; Determination; Counterfeiting; GC-MS; Residue; Dosage form; Tablet; Hard capsule; Solvent; Quantitative analysis
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2012.05.022

► A fast headspace-GC–MS method was developed for residual solvent analysis. ► The quantitative analysis was validated for 10 solvents applying the total error approach. ► All relative expanded uncertainties were around 5%. ► The method was applied for the analysis of relative solvents in counterfeit tablets and capsules.
A fast headspace GC–MS method was developed and validated for the detection and quantification of residual solvents of all three ICH-classes in counterfeit tablets and capsules. The method was validated for 10 solvents, selected based on an initial screening of counterfeit medicinal products. The considered solvents were ethanol, 2-propanol, acetone, ethylacetate, chloroform, carbon tetrachloride, benzene, toluene, dichloromethane and ethylbenzene. The proposed method uses a Phenomenex 624 capillary column (60m×0.32mm; 1.8μm film thickness) (Phenomenex, Torrance, USA) with an oven temperature program from 60°C (held for 5min) to 270°C at 25°C/min. 270°C is held for 10min. The total run time is 23.4min.
The obtained method was fully validated by applying the “total error” profile. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were smaller than 5%, the β-expectation tolerance limits did not exceed the acceptance limits of ±10% and the relative expanded uncertainties were acceptable for all of the considered components.
A method was obtained for the screening and quantification of residual solvents in counterfeit tablets and capsules, which will allow a fast screening of these products for the presence of residual solvents.