LC-MS in Drug Analysis Methods and Protocols
Liquid-Chromatography-Mass-Spectrometry procedures have been shown to be successful when applied to drug development and analysis. LC-MS in Drug Analysis: Methods and Protocols provides detailed LC-MS/MS procedures for the analysis of several compounds of
- PDF / 408,851 Bytes
- 10 Pages / 504.57 x 720 pts Page_size
- 73 Downloads / 162 Views
1. Introduction Amphetamine-type stimulants (ATSs) are a broad class of substances that, structurally, have a phenethylamine backbone. Changes to the side chain impart greater or lesser effects to the molecule in respect to pharmacological and toxicological
Loralie J. Langman and Christine L.H. Snozek (eds.), LC-MS in Drug Analysis: Methods and Protocols, Methods in Molecular Biology, vol. 902, DOI 10.1007/978-1-61779-934-1_9, © Springer Science+Business Media, LLC 2012
105
106
R.A. Middleberg and J. Homan
actions, although not necessarily uniformly (1). Additionally, changes to the phenyl moiety, e.g., addition of a dioxy bridge, can significantly affect the pharmacological and toxicological actions of the substance compared to the classic phenethylamine structure (2). These compounds have been used therapeutically for many years in the treatment of hyperactivity disorders and to facilitate weight loss. Additionally, other therapeutic uses of some of the ATSs exist, e.g., selegiline for Parkinson’s disease and dementia (3) or pseudoephedrine for nasal congestion. Not all of the amphetamines have therapeutic uses. In this respect, both licit and illicit amphetamines are subject to abuse, which can lead to addiction. Based on their abuse and addiction properties as well as a lack of, or limited, medical use, many of the amphetamines are classified in the United States as schedule I and II controlled substances (4). Common toxicological effects of amphetamines include hypertension, arrhythmia, excitability, aggressiveness, psychoses, cardiovascular accidents, coma, and death. Additionally, amphetamines can cause hallucinations. It should be noted, however, that not all adverse effects are observed with all compounds in this class of agents, and some adverse effects, e.g., “formication,” may be limited to certain amphetamines (5, 6). The analysis of ATSs is long-standing in toxicology. Some of the earlier methods of analysis, e.g., spectrophotometry, have given way to more specific methods based on mass spectrometry. However, due to their lack of characteristic or significant fragmentation, many of the amphetamines are a challenge even through mass spectrometric means of analysis. In gas chromatography–mass spectrometry (GC–MS), many of the amphetamines require derivatization to facilitate analysis (7). Further, in addition to sample preparation issues, it has been demonstrated that injection port chemistry in GC can lead to misleading results with some members of the amphetamine class (8). To circumvent these issues, liquid chromatography-mass spectrometry (LC-MS/ MS) offers the promise of a simpler sample preparation procedure and fewer analytical concerns. For example, no derivatization is needed in LC-MS/MS and given the softer ionization process, more distinctive fragmentation can be taken advantage of to aid in the qualitative and quantitative aspects of the analysis. Described herein is an LC-MS/MS technique for the analysis of 14 amphetamines in blood, serum/plasma, and urine using isotope dilution for the
Data Loading...
