High-efficiency sample preparation with dimethylformamide for multi-element determination in pharmaceutical materials by ICP-AES.

The pressure to reduce cycle times of sample analysis has made it increasingly important to improve sample throughput during pharmaceutical process development. For ICP-based analyses, sample preparation is often the bottleneck of the entire analytical scheme due to the tedious digestion procedure and lacking a universal diluent for organic compounds. In this work, N,N-dimethylformamide (DMF) was used as a "universal" organic diluent so that the sample preparation can be simplified as a "dilute-and-shoot" procedure. An optimized interface with a commercial membrane desolvation unit was implemented, which enabled the introduction of organic solvents into an ICP-AES without organic loading. Mixed standard solutions of 15 elements (Al, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pd, Pt, Rh, Ru, W, Zn, and Zr), which covered the majority of processing metals routinely monitored in pharmaceutical development, were prepared for the study and stability of each element in a multi-element DMF solution was investigated. It was found that the addition of a stabilizing agent (EDTA) was necessary to ensure that all the elements at concentrations of 0.10-0.50 microg/mL remained physically stable in solution (recovery better than 95%) for 2 weeks. It was also important to use an internal standard (yttrium) in order to compensate for signal drift and matrix effects from different sample matrices. A 2-10-fold increase of sensitivity (due to enhanced analyte transport efficiency) and acceptable levels of precision (RSD<3%) and recoveries (91-111%) were achieved. The LOQs of all 15 elements were less than 10 microg/L in the solution, which translates to less than 5 microg/g or microg/mL in pharmaceutical samples tested. This technique would minimize the effort required for sample preparation, thus reducing the cycle time by approximately 60-90% in the entire analytical scheme for samples that are difficult to be dissolved in nitric acid. This will provide opportunities for a new level of sample handling and automation for metal analysis in pharmaceutical process development.

High-throughput metal screening in pharmaceutical samples by ICP-MS with automated flow injection using a modified HPLC configuration.

There is growing pressure in pharmaceutical research and development to increase sample throughput and turnaround time for metal analysis. This need is especially pronounced when a large number of samples must be analyzed to support rapid remediation of metal contamination problems. In this study we describe the utilization of an HPLC-ICP-MS system in automated flow injection (FI) mode for the rapid assessment of metal (palladium, rhodium, chromium, etc.) concentration. The system consists of an HPLC standard or well-plate autosampler, a novel interface (consisting of a desolvating unit, an eluent splitter and a built-in peristaltic pump) and the ICP-MS instrument. This configuration ensures a fully automatic process and is well suited for standardization. The interface can be easily switched to adapt to HPLC eluents or FI introduction for speciation or flow injection analysis. The use of the well-plate autosampler decreases sample injection cycle time and adds flexibility to the system by allowing direct analysis with little or no sample preparation. The FI-ICP-MS method provides a means for high-throughput metal screening with unprecedented speed. Other advantages of the method include automatic analysis of microliter sample volumes, fast inter-sample washout and reduced reagent consumption.

Identification and characterization of isomeric intermediates in a catalyst formation reaction by means of speciation analysis using HPLC-ICPMS and HPLC-ESI-MS.

Information on chemical speciation is much needed in mechanistic and kinetic studies on catalyst formation processes in pharmaceutical research. Speciation analysis was applied to the identification and quantification of various rhodium species involved in a ligand exchange process leading to formation of catalyst dirhodium(II) tetrakis[methyl 2-oxopyrrolidin-5(S)-carboxylate]. Inductively coupled plasma mass spectrometry (ICPMS) was used as an element-specific detector following species separation by reversed-phase high-performance liquid chromatography (RP-HPLC), and electrospray ionization mass spectrometry (ESI-MS) was used for species identification and confirmation. A novel interface between the HPLC and ICPMS, which consisted of an eluent splitter, a desolvation unit, and the ICPMS built-in peristaltic pump, enabled the use of RP-HPLC with gradient elution and up to 100% organic components in the LC eluent without organic loading in the plasma. A variety of reaction intermediates were identified and quantified along the pathway to formation of the desired product, including isomeric di-, tri-, and tetrasubstituted species previously believed to be absent. This has provided new insights into the mechanism and kinetics of the reaction. The combination of HPLC-ICPMS and HPLC-ESI-MS has proven to be a valuable tool for the investigation of species evolution in catalyst formation process.

Determination of ruthenium in pharmaceutical compounds by graphite furnace atomic absorption spectroscopy.

A graphite furnace atomic absorption (GFAA) spectrometric method for the determination of ruthenium (Rh) in solid and liquid pharmaceutical compounds has been developed. Samples are dissolved or diluted in dimethyl sulfoxide (DMSO) without any other treatment before they were analyzed by GFAA with a carefully designed heating program to avoid pre-atomization signal loss and to achieve suitable sensitivity. Various inorganic and organic solvents were tested and compared and DMSO was found to be the most suitable. In addition, ruthenium was found to be stable in DMSO for at least 5 days. Spike recoveries ranged from 81 to 100% and the limit of quantitation (LOQ) was determined to be 0.5 microg g(-1) for solid samples or 0.005 microg ml(-1) for liquid samples based a 100-fold dilution. The same set of samples was also analyzed by ICP-MS with a different sample preparation method, and excellent agreement was achieved.

Direct determination of metals in organics by inductively coupled plasma atomic emission spectrometry in aqueous matrices.

A simple method for the simultaneous determination of up to 21 elements in organic matrices is proposed. Organic samples are simply dispersed in concentrated nitric acid by sonication, and the resulting emulsions/suspensions are directly aspirated into an inductively coupled plasma atomic emission spectrometer (ICP-AES) calibrated with aqueous standards for analysis. Proof of concept was provided by the excellent recoveries for the analysis of a 21-element metallo-organic standard. In addition, the results obtained using this method for a waste oil sample compared favorably with those from a method that utilized microwave digestion for sample preparation. Comparable results were also obtained by dilution in an organic solvent followed by ICP-AES analysis with an ultrasonic nebulizer equipped with a membrane desolvator. Furthermore, the viability and validity of this method were confirmed by the analysis of the National Institute of Standards and Technology standard reference material 1084a Wear-Metals in Lubricating Oil. Spike recoveries ranged from 83 to 105% and the limits of quantitation were 6 microg g(-1) or less for all the elements analyzed.