An important role of the clinical toxicology laboratory is to provide continuous diagnostic testing for patients with altered mental status and for other medical indications. To meet these needs, we have developed a new Gas Chromatography-Mass Spectrometry (GC-MS) platform that facilitates routine screening and automated reporting of 212 drugs by laboratory technologists around the clock without the need to sign out by an on-site mass spectrometry-trained toxicologist. The platform uses a programmable temperature vaporizer (PTV) injector for large sample volume injection and the free software Automated Mass Spectral Deconvolution and Identification System (AMDIS) for data reduction and spectral matching that facilitates rapid library searching and analyte identification. Method comparison with 118 patient samples demonstrated that this platform and data searching algorithm independently provided improvements in sensitivity compared to an established GC-MS platform. Further examination of the role of the data processing software and the in-house databases used in the established versus the new platform demonstrated that the improved analytical sensitivity of the new platform was attributed to both the technical superiority of the new GC-MS instrumentation and the use of AMDIS in conjunction with the newly generated in-house library for data processing. 1. Introduction Screening patients for toxins, including prescription and/or illegal drugs, is a key function of a clinical toxicology lab. In our hospital, we perform comprehensive toxicological screening of a patient population with a high pretest probability of use, abuse, and overdose of prescription, over-the-counter (OTC), and illegal drugs using a combination of immunoassays and Gas Chromatography-Mass Spectrometry (GC-MS). Clinicians are advised to use this comprehensive urine drug screen to evaluate possible accidental or intentional overdose or poisoning, to assess the type of prescribed and/or illicit drugs used by a patient, or to determine the cause of acute drug toxicity. The assay is also used in specific clinical contexts to investigate whether specific drugs are present in a patient’s urine before starting a medical procedure. Most clinical toxicology laboratories employ one or more of a variety of analytical and immunological approaches such as Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) [1–4], GC-MS [5, 6], and immunoassay (i.e., EMIT) [7] to screen patient urine samples for a variety of drugs. While immunoassays are fast and fully automated, the technique is prone to
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