Application of diode array detectors for solute identification in toxicological analysis

Summary The possibilities and limitation of automated solute identification via UV/VIS spectroscopy in HPLC are demonstrated and applications in toxicologic analysis are described. A standard isocratic system is used. The influence of various chromatographic parameters on retention time is shown. A retention time window of ±15% is required. In addition to retention time, derived spectral data are calculated (minima and maxima of derivatives, area counts under standardized spectral ranges, absorption at various wavelength) and used for positive solute identification. It is possible to identify solutes with a high degree of certainty in urine and plasma if their concentration is at least 10 ppm.     

Identification,control strategies,and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors’ intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.     

Direct drug analysis from oral fluid using medical swab touch spray mass spectrometry

Fourteen common drugs of abuse were identified in spiked oral fluid (ng mL⁻¹ levels), analyzed directly from medical swabs using touch spray mass spectrometry (TS-MS), exemplifying a rapid test for drug detection. Multiple stages of mass analysis (MS² and MS³) provided identification and detection limits sought by international forensic and toxicological societies, Δ⁹-THC and buprenorphine excluded. The measurements were made using a medical swab as both the sampling probe and means of ionization. The adaptation of medical swabs for TS-MS analysis allows non-invasive and direct sampling of neat oral fluid. Data acquisition was rapid, seconds per drug, and MS³ ensured reliable identification of illicit drugs. The reported data were acquired to investigate (i) ionization of common drugs from commercial swabs, (ii) ion intensity over spray duration, and (iii) dynamic range, all as initial steps in development of a quantitative method. The approach outlined is intended for point-of-care drug testing using oral fluid in clinical applications as well as in situ settings, viz. in forensic applications. The proof-of-concept results presented will require extension to other controlled substances and refinement in analytical procedures to meet clinical/legal requirements.     

The use of amperometric oxygen electrodes for measurements of enzyme reactions

Amperometric oxygen electrodes are useful transducers for enzymatic analyses. One must, however, account for contributions from oxygen incorporation or depletion caused by sample introduction, stirring and diffusion, or non-enzymatic reactions, as well as for instrumental response time. Examples of various characteristics of these contributions are shown and discussed from a theoretical basis.     

Toxicological problems relating to changes in the environment

Assessment of the toxicological risk from foreign substances in the environment is based on the determination of action thresholds below which effects injurious to health no longer occur, even with life-long intake. According to the latest theories it is likely that such thresholds exist even for “irreversible” (carcinogenic, mutagenic) effects. However, the difficulties besetting the determination of threshold values by experimental or epidemiological methods still appear to be virtually insuperable. The problems are both quantitative (excessive numbers of animals and observations required) and qualitative (poor predictability of effects owing to substantial differences in biological reactivity between species). Neither animal experiments nor experience with human subjects can guarantee total security from toxic effects. Legislative measures designed to restrict the introduction of chemical substances into the environment must therefore be based on compromise. Scientists must be consulted, but ultimately the decisions must be political, and politicians have to assume the responsibility for them.     

Mass spectrometric approaches in impaired driving toxicology

Driving under the influence of prescribed or illegal drugs increases the risk of having road accidents, just like driving under the influence of alcohol. In forensic toxicology, an increasing number of blood samples must be analyzed for drugs. Immunoassays tailored for a limited number of drugs (of abuse) are usually applied as prescreening tests at the roadside and/or in the laboratory. However, many other common drugs, such as anesthetics, antidepressants, antiepileptics, antihistamines, newer designer drugs, herbal drugs, neuroleptics (antipsychotics), opioids, or sedative-hypnotics, can also impair drivers. Therefore, this paper reviews multianalyte single-stage and tandem gas or liquid chromatography–mass spectrometry (GC-MS or LC-MS) procedures for the screening, identification, and validated quantification of such drugs in blood that have been reported since 2003. Basic information about the biosample assayed, workup, chromatography, the mass spectral detection mode, and validation data is summarized in tables. The pros and cons of the reviewed procedures are critically discussed, particularly with respect to their probable usefulness in impaired driving toxicology. Parts of this review were presented as a plenary lecture at T2007, the joint meeting of the International Council on Alcohol, Drugs, and Traffic Safety (ICADTS) and The International Association of Forensic Toxicologists (TIAFT), Seattle (WA), August 26–30, 2007.     

Proficiency testing schemes for therapeutics and toxicology

 This report addresses the proposition: current proficiency testing (PT) schemes for therapeutics and toxicology can easily engender complacency. The proposition was based on the premise that there are substantial between-laboratory differences and objectives in the supply of services for the measurement of drugs, as a result of which it is difficult to design PT schemes which adequately cover the requirements of all laboratories. Thus, acceptable performance in a PT scheme may lead participants to consider that they have tested their procedures more rigorously than is the case. Four areas, validity of the PT scheme, PT material, frequency of testing and acceptance criteria are examined. Received: 15 April 2000 · Accepted: 15 April 2000