This chapter reviews the selection of chromatography-mass spectrometry methods for the analysis of organophosphorus pesticides, pyrethroid insecticides, carbamates, and phenylureas. Options with different GC-MS, GC-MS/MS, and LC-MS/MS methods will be discussed for inclusion of the targeted pesticides. In addition, methods for the analysis of metabolites of these chemical classes of pesticides are investigated, including the feasibility of simultaneous analysis with parent pesticides. In some cases, a targeted approach is required for the analyses of metabolites. These methods apply to a wide variety of sample matrices including environmental (air, water, and soil), food (fruits, vegetation, or food products), and biological samples (urine and blood). The focus of the chapter is on MS detection approaches with consideration of the chromatographic separation conditions as required. A short discussion of multiresidue analysis methods and/or where feasible, other chemical classes or selected pesticides from these chemical classes can be analyzed in existing methods is included.

Leachable testing for finished pharmaceutical products is an important part of the regulatory filing and is under more regulatory scrutiny than ever before. Leachable testing for multiple finished drug products such as biologics, large volume parenterals, and polymer-based finished products requires analysis at trace levels with a high level of confidence. A high level of analytical expertise and top-of-the-line analytical instrumentation is required for work at trace levels. (The definition of trace level analytical testing has not been accurately defined; however, to have a sense of the “trace-level”-associated testing issues, we are arbitrarily assigning levels below 100 ng/mL as trace level and below 1 ng/mL as ultra-trace level in this paper). Leachable testing ideally should be performed on a targeted list of analytes compiled from an extractable study and an extractable and leachable correlation study, along with a general non-targeted screening evaluation to avoid any undetected leachables. For targeted screening, analytical testing is more straightforward and can typically detect targets at ppb or sub-ppb levels without issue. However, for a general screening method, this can be difficult, and many times requires special sample preparation combined with high-resolution accurate-mass detection. Case studies will be presented to demonstrate the importance of high-performance and highly sensitive screening methods in detecting unexpected leachables, and in supporting related quality investigations. The importance of well-designed and executed system suitability will also be discussed in this paper.