title: High-efficiency sample preparation with dimethylformamide for multi-element determination in pharmaceutical materials by ICP-AES.
abstract: 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.
authors.affiliation: Merck Research Laboratories, Merck & Co, Inc, RY818-C102, PO Box 2000, 126 E Lincoln Ave, Rahway, NJ 07065, United States. qiang_tu@merck.com
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tu
authors.forename: Tiebang
authors.initials: T
authors.lastname: Wang
authors.forename: Vincent
authors.initials: V
authors.lastname: Antonucci
mesh_terms: D002138:Calibration; D004126:Dimethylformamide / Q000032:analysis*; D057230:Limit of Detection; D008670:Metals / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012995:Solubility; D013054:Spectrophotometry, Atomic / Q000295:instrumentation / Q000379:methods*
chemical_list: D008670:Metals; D004364:Pharmaceutical Preparations; D004126:Dimethylformamide