Improving gas chromatographic determination of residual solvents in pharmaceuticals by the combined use of headspace solid-phase microextraction and isotopic dilution

• Published in: Journal of Chromatography A Vol. 915; no. 1; pp. 209 - 216
• Main Authors: Coran, Silvia A., Giannellini, Valerio, Furlanetto, Sandra, Bambagiotti-Alberti, Massimo, Pinzauti, Sergio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27.04.2001; Elsevier
• Subjects: Analysis; Biological and medical sciences; Calibration; General pharmacology; Isotopes; Ketoprofen; Ketoprofen - chemistry; Medical sciences; Pharmacology. Drug treatments; Profens; Reproducibility of Results; Sensitivity and Specificity; Solvents - analysis; Isotopic dilution; Pharmaceutical analysis; Experimental design; Profens; Ketoprofen; Solid phase extraction; Chemical analysis; Flame ionization detector; Raw materials; Optimization; Chemical enrichment; Sample preparation; Arylpropionic acid derivatives; Quantitative analysis; Trace analysis; Coupled method; Toluene; Isotope dilution; Capsule; Operating conditions; Non steroidal antiinflammatory agent; Solid phase microextraction; Gas chromatography; Organic solvent; Residue; Quality control; Cyclohexane; Dosage form; Headspace; Factorial design; Mass spectrometry; Chemometrics
• ISSN: 0021-9673
• DOI: 10.1016/S0021-9673(01)00658-6

Cyclohexane and toluene were gas chromatographically determined via headspace solid-phase microextraction both in ketoprofen drug substance and ketoprofen capsules by a procedure relying on isotopic dilution (ID), an analytical tool derived from mass spectrometry (MS). This approach, using an internal standard method, gave mean precision and accuracy (RSD 2.56%, 2.97% and bias 0.21%, −0.99% for cyclohexane and toluene, respectively) not obtainable by the more commonly used external standard ones in the presence of real sample matrices. Optimisation of the operative conditions was also supported by experimental design. More generally, the proposed method, exploiting ID without resort to the costly MS instrumentation, could be recommended whenever opportune deuterated analogues of the target analytes and GC capillary columns able to separate all the peaks involved are ready available on the market.