One of the more important applications in the pharmaceutical and personal care industries is the determination of degradation products in volatile and semivolatile compounds. The conventional approaches to these studies often utilize time-consuming and labor-intensive techniques in conjunction with potentially hazardous solvents. A new approach developed in our laboratory using solid-phase microextraction (SPME) in conjunction with gas chromatography-mass spectrometry (GC/MS) to determine degradation products for volatile and semivolatile organic compounds is described. The approach was evaluated by the measurement of diphenhydramine hydrochloride, a known over-the-counter (active) pharmaceutical product. Aqueous solutions of diphenhydramine HCl were subjected to stress and subsequently examined using SPME-GC/MS. The hydrolysis degradation products benzhydrol, benzophenone, and dimethylaminoethanol were detected. Solid diphenhydramine was thermally stressed and subsequently examined by headspace SPME/GC-MS. The thermal degradation products detected were dimethylaminoethanol, diphenylmethane, diphenylchloromethane, benzhydrol, and benzophenone. These results were in agreement with degradation studies in the literature performed on diphenhydramine HCl using conventional approaches. SPME-GC/MS was then used to determine the acid hydrolysis degradation product for a cosmetic preservative iodopropynyl butyl carbamate (3-iodo-2-propynyl-n-butyl carbamate) also known as IPBC. SPME/GC-MS analysis of an acid-stressed IPBC solution yielded evidence of the compound 3-iodo-2-chloro-2-propenyl-n-butyl carbamate, indicative of addition of HCl across the triple bond of IPBC. © 2001 John Wiley & Sons, Inc. J Micro Sep 13: 1–7, 2001