Determination of triphenylphosphine oxide in active pharmaceutical ingredients by hollow-fiber liquid-phase microextraction followed by reversed-phase liquid chromatography

• Published in: Journal of Chromatography A Vol. 1127; no. 1; pp. 147 - 153
• Main Authors: Richoll, Stephen M., Colón, Ivelisse
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-09-2006; Elsevier
• Subjects: Active pharmaceutical ingredients; Analysis; Biological and medical sciences; Chemical Fractionation - instrumentation; Chemical Fractionation - methods; Chromatography, High Pressure Liquid; General pharmacology; Impurity analysis; Liquid-phase microextraction; LPME; Medical sciences; Organophosphorus Compounds - analysis; Organophosphorus Compounds - chemistry; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; TPPO; Triphenylphosphine oxide; Liquid-phase microextraction; TPPO; Impurity analysis; Active pharmaceutical ingredients; Triphenylphosphine oxide; LPME; Chemical analysis; Impurity; HPLC chromatography; Purity control; Solvent extraction; Phosphorus Organic compounds; Chemical enrichment; Tertiary phosphine oxide; Sample preparation; Hollow fiber; Trace analysis; Validation; Liquid liquid extraction; Liquid phase microextraction; Microassay; Reversed phase chromatography; Ultraviolet detector; Quality control; Active ingredient
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2006.06.004

A versatile procedure has been developed and validated for the determination of triphenylphosphine oxide (TPPO) at low levels in various active pharmaceutical ingredients (APIs). This procedure incorporates the use of the novel hollow-fiber liquid-phase microextraction (LPME) for the measurement of this potential process-related impurity in aqueous solutions of APIs. A small volume (40
μL) of 1-octanol contained within a hollow polypropylene fiber is used for the extraction of TPPO from low pH aqueous API solutions. More than a 100-fold increase in the TPPO concentration is obtained without additional evaporation of the extract. Experimental parameters of the extraction procedure were investigated to optimize extraction efficiency and minimize sample matrix interference. Using HPLC/UV as the end analysis technique, the procedure was validated for TPPO in the concentration range of 3–16
μg/L with an API present at 1500
mg/L. The versatility of the method was demonstrated by applying the procedure to the analysis of APIs with different molecular structures. This simple LPME procedure is inexpensive and offers appropriate sensitivity for the intended use while providing several advantages over other analysis methods for pharmaceutical samples.