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

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 microL) 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 microg/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.

Determination of methyl and ethyl esters of methanesulfonic, benzenesulfonic and p-toluenesulfonic acids in active pharmaceutical ingredients by solid-phase microextraction (SPME) coupled to GC/SIM-MS.

The development, optimization and validation of an extraction method for methyl and ethyl esters of various sulfonic acids is presented. The extraction and determination of these esters in active pharmaceutical ingredients (APIs) was accomplished using solid-phase microextraction coupled to GC/MS in the SIM mode. The factors affecting the extraction efficiency are discussed. This method was validated as a limits test and allows the determination of the sulfonic esters at the 5 ppm level in APIs. The method proved to be reproducible (%R.S.D.s less than 6%) and suitable for use with external standard quantitation, and also met basic validation requirements. This method offers numerous advantages over liquid-liquid extraction methods and was also compared to other extraction techniques such as solid-phase extraction (SPE) and liquid-phase microextraction (LPME) also being developed in our laboratories.