Check out our New Publishers' Select for Free Articles

Analytical and Bioanalytical Chemistry (v.388, #7)

Analytical toxicology by Hans H. Maurer (pp. 1311-1311).

is Head of the Department of Experimental and Clinical Toxicology of Saarland University in Homburg. He has published over 130 original papers and 20 invited reviews on his main two areas of research, analytical toxicology (GC–MS, LC–MS) and metabolism of xenobiotics. He has received several international scientific awards for his outstanding scientific work, and in 2007 he was awarded the title of Doctor Honoris Causa by the University of Ghent.

Peter Rösner, Thomas Junge, Folker Westphal, Giselher Fritschi: Mass spectra of designer drugs including drugs, chemical warfare agents, and precursors by Hans H. Maurer (pp. 1313-1314).

Current role of liquid chromatography–mass spectrometry in clinical and forensic toxicology by Hans H. Maurer (pp. 1315-1325).

This paper reviews multi-analyte single-stage and tandem liquid chromatography–mass spectrometry (LC-MS) procedures using different mass analyzers (quadrupole, ion trap, time-of-flight) for screening, identification, and/or quantification of drugs, poisons, and/or their metabolites in blood, plasma, serum, or urine published after 2004. Basic information about the biosample assayed, work-up, LC column, mobile phase, ionization type, mass spectral detection mode, and validation data of each procedure is summarized in tables. The following analytes are covered: drugs of abuse, analgesics, opioids, sedative-hypnotics, benzodiazepines, antidepressants including selective-serotonin reuptake inhibitors (SSRIs), herbal phenalkylamines (ephedrines), oral antidiabetics, antiarrhythmics and other cardiovascular drugs, antiretroviral drugs, toxic alkaloids, quaternary ammonium drugs and herbicides, and dialkylphosphate pesticides. The pros and cons of the reviewed procedures are critically discussed, particularly, the need for studies on matrix effects, selectivity, analyte stability, and the use of stable-isotope labeled internal standards instead of unlabeled therapeutic drugs. In conclusion, LC-MS will probably become a gold standard for detection of very low concentrations particularly in alternative matrices and for quantification in clinical and forensic toxicology. However, some drawbacks still need to be addressed and finally overcome. Photos of LC-MS apparatus and typical samples suitable for toxicological analysis

Keywords: Drug; Blood; Urine; Liquid chromatography–mass spectrometry; Toxicology

Current role of LC-MS in therapeutic drug monitoring by Franck Saint-Marcoux; François-Ludovic Sauvage; Pierre Marquet (pp. 1327-1349).

The role of liquid chromatography coupled with mass spectrometry (LC-MS) techniques in routine therapeutic drug monitoring activity is becoming increasingly important. This paper reviews LC-MS methods published in the last few years for certain classes of drugs subject to therapeutic drug monitoring: immunosuppressants, antifungal drugs, antiretroviral drugs, antidepressants and antipsychotics. For each class of compounds, we focussed on the most interesting methods and evaluated the current role of LC-MS in therapeutic drug monitoring.

Keywords: Therapeutic drug monitoring; Liquid chromatography; Mass spectrometry

Current role of LC–MS(/MS) in doping control by Mario Thevis; Wilhelm Schänzer (pp. 1351-1358).

Liquid chromatography–(tandem) mass spectrometry (LC–MS/MS) has revolutionized the detection assays used in doping control analysis over the last decade. New methods have enabled the determination of drugs that were formerly difficult to detect or undetectable at preceding sample concentrations, and complex and/or time-consuming procedures based on alternative chromatographic–mass spectrometric or immunochemical principles have been replaced by faster, more comprehensive and robust assays. A critical overview of the contributions of LC–MS(/MS) to sports drug testing is provided, including recent developments regarding low and high molecular weight drugs.

Keywords: Doping; Sport; Mass spectrometry; Criteria; Peptide; Protein

Current role of capillary electrophoretic/electrokinetic techniques in forensic toxicology by Franco Tagliaro; Federica Bortolotti; Jennifer P. Pascali (pp. 1359-1364).

The current application of capillary electrophoresis in forensic toxicology has been critically reviewed with special focus on the areas where this technique has shown real advantages over chromatographic methods. For example, capillary electrophoresis has been most successfully applied to the chiral analysis of some drugs of forensic interest, including amphetamines and their congeners. Another typical application field of capillary electrophoresis is represented by protein analysis. Recently, special interest has been paid to carbohydrate deficient transferrin (CDT), the most important biological marker of chronic alcohol abuse. Other specific applications of capillary electrophoresis of potential forensic toxicological concern are also discussed. The review includes 62 references.

Keywords: Capillary electrophoresis; Drug analysis; Forensic toxicology

New analytical strategies in studying drug metabolism by Roland F. Staack; Gérard Hopfgartner (pp. 1365-1380).

Identification and elucidation of the structures of metabolites play major roles in drug discovery and in the development of pharmaceutical compounds. These studies are also important in toxicology or doping control with either pharmaceuticals or illicit drugs. This review focuses on: new analytical strategies used to identify potential metabolites in biological matrices with and without radiolabeled drugs; use of software for metabolite profiling; interpretation of product spectra; profiling of reactive metabolites; development of new approaches for generation of metabolites; and detection of metabolites with increased sensitivity and simplicity. Most of the new strategies involve mass spectrometry (MS) combined with liquid chromatography (LC).

Keywords: Liquid chromatography; Mass spectrometry; Drug metabolism

Recent developments in extraction procedures relevant to analytical toxicology by Sarah M. R. Wille; Willy E. E. Lambert (pp. 1381-1391).

Sample preparation is an important step in the development of an analytical method but is often regarded as time-consuming, laborious work. Optimum sample preparation leads to enhanced selectivity and sensitivity, however, and reduces amounts of interfering matrix compounds, resulting in less signal suppression or enhancement. Recent developments in extraction techniques that could be of interest in clinical and forensic toxicology, for example liquid–liquid, solid-phase, and headspace extraction, are summarized in this review. The advantages and disadvantages of several extraction techniques are discussed, to enable the reader to choose an appropriate method of extraction for his or her application. Attention is paid to current trends in analytical toxicology, for example miniaturization, high throughput, and automation.

Keywords: Solid-phase extraction; Liquid–liquid extraction; Automation; Review; Gas chromatography; Liquid chromatography

Application of solid-phase microextraction in analytical toxicology by Fritz Pragst (pp. 1393-1414).

Solid-phase microextraction (SPME) is a miniaturized and solvent-free sample preparation technique for chromatographic–spectrometric analysis by which the analytes are extracted from a gaseous or liquid sample by absorption in, or adsorption on, a thin polymer coating fixed to the solid surface of a fiber, inside an injection needle or inside a capillary. In this paper, the present state of practical performance and of applications of SPME to the analysis of blood, urine, oral fluid and hair in clinical and forensic toxicology is reviewed. The commercial coatings for fibers or needles have not essentially changed for many years, but there are interesting laboratory developments, such as conductive polypyrrole coatings for electrochemically controlled SPME of anions or cations and coatings with restricted-access properties for direct extraction from whole blood or immunoaffinity SPME. In-tube SPME uses segments of commercial gas chromatography (GC) capillaries for highly efficient extraction by repeated aspiration–ejection cycles of the liquid sample. It can be easily automated in combination with liquid chromatography but, as it is very sensitive to capillary plugging, it requires completely homogeneous liquid samples. In contrast, fiber-based SPME has not yet been performed automatically in combination with high-performance liquid chromatography. The headspace extractions on fibers or needles (solid-phase dynamic extraction) combined with GC methods are the most advantageous versions of SPME because of very pure extracts and the availability of automatic samplers. Surprisingly, substances with quite high boiling points, such as tricyclic antidepressants or phenothiazines, can be measured by headspace SPME from aqueous samples. The applicability and sensitivity of SPME was essentially extended by in-sample or on-fiber derivatization. The different modes of SPME were applied to analysis of solvents and inhalation narcotics, amphetamines, cocaine and metabolites, cannabinoids, methadone and other opioids, fatty acid ethyl esters as alcohol markers, γ-hydroxybutyric acid, benzodiazepines, various other therapeutic drugs, pesticides, chemical warfare agents, cyanide, sulfide and metal ions. In general, SPME is routinely used in optimized methods for specific analytes. However, it was shown that it also has some capacity for a general screening by direct immersion into urine samples and for pesticides and other semivolatile substance in the headspace mode.

Keywords: Drug analysis by solid-phase microextraction; Headspace extraction; In-tube solid-phase microextraction; Sample preparation; Solid-phase microextraction; Volatile poisons

Bioanalytical procedures for determination of drugs of abuse in blood by Thomas Kraemer; Liane D. Paul (pp. 1415-1435).

Determination of drugs of abuse in blood is of great importance in clinical and forensic toxicology. This review describes procedures for detection of the following drugs of abuse and their metabolites in whole blood, plasma or serum: Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide, heroin, 6-monoacetylmorphine, morphine, morphine-6-glucuronide, morphine-3-glucuronide, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, ecgonine methyl ester, cocaethylene, other cocaine metabolites or pyrolysis products (norcocaine, norcocaethylene, norbenzoylecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine, ethyl ecgonine, ecgonine, anhydroecgonine methyl ester, anhydroecgonine ethyl ester, anhydroecgonine, noranhydroecgonine, N-hydroxynorcocaine, cocaine N-oxide, anhydroecgonine methyl ester N-oxide). Metabolites and degradation products which are recommended to be monitored for assessment in clinical or forensic toxicology are mentioned. Papers written in English between 2002 and the beginning of 2007 are reviewed. Analytical methods are assessed for their suitability in forensic toxicology, where special requirements have to be met. For many of the analytes sensitive immunological methods for screening are available. Screening and confirmation is mostly done by gas chromatography (GC)–mass spectrometry (MS) or liquid chromatography (LC)–MS(/MS) procedures. Basic information about the biosample assayed, internal standard, workup, GC or LC column and mobile phase, detection mode, and validation data for each procedure is summarized in two tables to facilitate the selection of a method suitable for a specific analytic problem.

Keywords: Drugs of abuse; Gas chromatography–mass spectrometry; Liquid chromatography–tandem mass spectrometry; Blood; Determination; Forensic toxicology

Bioanalytical procedures for determination of drugs of abuse in oral fluid by Nele Samyn; Marleen Laloup; Gert De Boeck (pp. 1437-1453).

Recent advances in analytical techniques have enabled the detection of drugs and drug metabolites in oral fluid specimens. Although GC–MS is still commonly used in practice, many laboratories have developed and successfully validated methods for LC–MS(–MS) that can detect a large number of compounds in the limited sample volume available. In addition, several enzyme immunoassays have been commercialized for the detection of drugs of abuse in oral fluid samples, enabling the fast screening and selection of presumably positive samples. A number of concerns are discussed, such as the variability in the volume of sample collected and its implications in terms of quantitative measurements, and the drug recoveries of the many different specimen collection systems on the market. Additional considerations that also receive attention are the importance of providing complete validation data with respect to analyte stability, matrix effect, and the choice of collection method.

Keywords: Drugs of abuse; Oral fluid; Analytical methods; Review

Bioanalytical procedures for monitoring in utero drug exposure by Teresa Gray; Marilyn Huestis (pp. 1455-1465).

Drug use by pregnant women has been extensively associated with adverse mental, physical, and psychological outcomes in their exposed children. This manuscript reviews bioanalytical methods for in utero drug exposure monitoring for common drugs of abuse in urine, hair, oral fluid, blood, sweat, meconium, amniotic fluid, umbilical cord tissue, nails, and vernix caseosa; neonatal matrices are particularly emphasized. Advantages and limitations of testing different maternal and neonatal biological specimens including ease and invasiveness of collection, and detection time frames, sensitivities, and specificities are described, and specific references for available analytical methods included. Future research involves identifying metabolites unique to fetal drug metabolism to improve detection rates of in utero drug exposure and determining relationships between the amount, frequency, and timing of drug exposure and drug concentrations in infant biological fluids and tissues. Accurate bioanalytical procedures are vital to defining the scope of and resolving this important public health problem.

Keywords: In utero; Drug testing; Cord blood; Meconium; Umbilical cord; Prenatal drug exposure

Bioanalytical procedures for detection of chemical agents in hair in the case of drug-facilitated crimes by Pascal Kintz (pp. 1467-1474).

The use of a drug to modify a person’s behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused alarm in the general public. The drugs involved can be pharmaceuticals, such as benzodiazepines (flunitrazepam, lorazepam, etc.), hypnotics (zopiclone, zolpidem), sedatives (neuroleptics, some anti-H1) or anaesthetics (γ-hydroxybutyrate, ketamine), drugs of abuse, such as cannabis, ecstasy or LSD, or more often ethanol. To perform successful toxicological examinations, the analyst must follow some important rules: (1) obtain as soon as possible the corresponding biological specimens (blood and urine); (2) collect hair about 1 month after the alleged event; (3) use sophisticated analytical techniques (gas or liquid chromatography coupled to tandem mass spectrometry, MS/MS, headspace gas chromatography); and (4) take care in the interpretation of the findings. Drugs used to facilitate sexual assaults can be difficult to detect (active products at low doses, chemical instability), possess amnesic properties and can be rapidly cleared from the body (short half-life). In these situations, blood or even urine can be of low interest. This is the reason why some laboratories have developed an original approach based on hair testing. Hair was suggested as a valuable specimen in situations where, as a result of a delay in reporting the crime, natural processes have eliminated the drug from typical biological specimens. While there are a lot of papers that have focused on the identification of drugs in hair following chronic drug use, those dealing with a single dose are very scarce. The experience of the author and a review of the existing literature will be presented for cases involving benzodiazepines, hypnotics, γ-hydroxybutyrate and various sedatives or chemical weapons. The expected concentrations in hair are in the low picogram/milligram range for most compounds. Hair analysis may be a useful adjunct to conventional drug testing in sexual assault. It should not be considered as an alternative to blood and urine analyses, but as a complement. This approach may find useful applications, but the definition of legally defensible cutoff values would require much more data. MS/MS technologies appear as a prerequisite in drug-facilitated cases.

Keywords: Hair; Drug-facilitated crime; Drug-facilitated sexual assault; Liquid chromatography–mass spectrometry

Analytical pitfalls in hair testing by Frank Musshoff; Burkhard Madea (pp. 1475-1494).

This review focuses on possible pitfalls in hair testing procedures. Knowledge of such pitfalls is useful when developing and validating methods, since it can be used to avoid wrong results as well as wrong interpretations of correct results. In recent years, remarkable advances in sensitive and specific analytical techniques have enabled the analysis of drugs in alternative biological specimens such as hair. Modern analytical procedures for the determination of drugs in hair specimens—mainly by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS)—are reviewed and critically discussed. Many tables containing information related to this topic are provided.

Keywords: Bioanalytical methods; Drug monitoring; Drug screening; Forensics; Toxicology

Requirements for bioanalytical procedures in postmortem toxicology by Olaf H. Drummer (pp. 1495-1503).

The application of analytical techniques in postmortem toxicology is often more difficult than in other forms of forensic toxicology owing to the variable and often degraded nature of the specimens and the diverse range of specimens available for analysis. Consequently, analysts must ensure that all methods are fully validated for the particular postmortem specimen(s) used. Collection of specimens must be standardized to minimize site-to-site variability and should if available include a peripheral blood sample and at least one other specimen. Urine and vitreous humor are good specimens to complement blood. In some circumstances solid tissues such as liver are recommended as well as gastric contents. Substance-screening techniques are the most important element since they will determine the range of substances that were targeted in the investigation and provide initial indication of the possible role of substances in the death. While immunoassay techniques are still commonly used for the most common drugs-of-abuse, chromatographic screening methods are required for general unknown testing. These are still predominately gas chromatography (GC) based using nitrogen/phosphorous detection and/or mass spectrometry (MS) detection, although some laboratories are now using time-of-flight MS or liquid chromatography (LC)–MS(MS) to cover a sometimes more limited range of substances. It is recommended that laboratories include a second chromatographic method to provide coverage of acidic and other substances not readily covered by a GC-based screen when extracts do not include all physiochemical types. This may include a gradient high-performance liquid chromatography (HPLC) photodiode array method, or better LC-MS(MS). Substance-specific techniques (e.g., benzodiazepines, opiates) providing a second form of identification (confirmation) are now divided between GC-MS(MS) and LC-MS(MS) procedures. LC-MS(MS) has taken over from many methods for the more polar compounds previously used in HPLC or in GC methods requiring derivatization. Analysts using LC-MS will need to obtain clean extracts to avoid poor and variable sensitivity caused by background suppression of the signal. Isolation techniques in postmortem toxicology tend to favor liquid extraction; however solid-phase extraction and solid-phase microextraction methods are available for many analytes.

Keywords: Postmortem toxicology; Bioanalytical methods; Minimum standards; Artifacts; Systematic toxicological analysis; Initial testing

Stability of analytes in biosamples—an important issue in clinical and forensic toxicology? by Frank T. Peters (pp. 1505-1519).

Knowledge of the stability of drugs in biological samples is important for the interpretation of toxicological findings. This paper reviews data on the stability of drugs in blood, plasma, or serum. Since such data have already been reviewed for classic drugs of abuse, the focus here is on newer drugs of abuse and on therapeutic drugs. Key information about the conditions of the stability experiments will be provided and the following drugs or drug classes are covered: amphetamines, amphetamine-derived, piperazine-derived, and phenethylamine-derived designer drugs, antidepressants, neuroleptics, anti-HIV drugs, antiepileptics, cardiovascular drugs, and others. In addition, aspects of stability experiments and their evaluations are discussed. The data presented show that the majority of drugs are stable in blood, plasma, or serum samples under the conditions usually encountered in a clinical or forensic toxicology laboratory. Instability usually only occurs for drugs carrying ester moieties, sulfur atoms, or other easily oxidized or reduced structures. Nevertheless, clinical or forensic specimens should always be stored at least in the refrigerator and preferably at −20 °C or lower to avoid any degradation. Finally, results obtained from biosamples that have been stored at room temperature for a longer time should be interpreted with great care and partial degradation should always be considered.

Keywords: Drug; Stability; Toxicology; Blood; Plasma; Serum

Procedures for monitoring recombinant erythropoietin and analogues in doping control by Jordi Segura; José A. Pascual; Ricardo Gutiérrez-Gallego (pp. 1521-1529).

The present report summarizes the main analytical strategies developed to identify the presence of recombinant erythropoietin (EPO) administered as a doping agent. Indirect evidence is based on the analysis of blood parameters (haemoglobin, haematocrit, reticulocytes, macrocytes, etc.) and serum markers (concentration of EPO and serum transferrin receptors, etc.). The problem of intertechnique comparison for reliable results evaluation is emphasized, especially for serum markers. Charge differences between isoforms of recombinant EPO and native urinary EPO are the grounds for the isoelectric focusing–double blotting–chemiluminescence detection method presently approved for doping control. Works addressing its advantages and limitations are presented and commented on. The chemical bases of the differential detection are highlighted and some future approaches for detection are also presented. The appearance and detectability of EPO analogues and mimetics susceptible for abuse are also addressed.

Keywords: Erythropoietin; Detection; Blood; Urine; Analogues; Mimetics

Anti-EPO and anti-NESP antibodies raised against synthetic peptides that reproduce the minimal amino acid sequence differences between EPO and NESP by E. Giménez; C. de Bolós; V. Belalcazar; D. Andreu; E. Borrás; B. G. De la Torre; J. Barbosa; J. Segura; J. A. Pascual (pp. 1531-1538).

Erythropoietin (EPO) is a hormone that regulates red blood cell production. Recombinant human EPO (rHuEPO) and NESP (novel erythropoiesis stimulating protein) have been produced for therapeutic purposes and also to improve sports performance. The primary sequences of rHuEPO and NESP differ by just five amino acids. Due to the high homology, no antibodies that are able to discriminate between both molecules have been obtained until now. The aim of the present work was to design synthetic peptides corresponding to the sequence that differs between EPO and NESP (87–90aa), that can then be used as immunogens to develop specific rabbit polyclonal antibodies for selectively detecting EPO and NESP. Three peptides were synthesized: EPO (81–95), NESP (81–95), and NESP (86–104), and these were coupled to KLH and OVA for immunization and screening purposes, respectively. The sera obtained were tested by ELISA on synthetic peptide–OVA conjugates and purified by immunoaffinity chromatography against the corresponding synthetic peptide. The specific purified antibodies were characterized by ELISA, SDS-PAGE, and isoelectric focusing, followed by western blot. Antisera raised against EPO (81–95) recognized rHuEPO but not NESP. In contrast, anti-NESP (84–106) sera gave a specific anti-NESP response only after immunoaffinity purification on a NESP (86–91) column. An efficient strategy for generating specific antibodies against EPO and NESP can be achieved by selecting suitable synthetic peptides. The antibodies obtained are able to differentiate between rHuEPO and NESP, and may be particularly useful for screening purposes in both therapeutic and antidoping contexts.

Keywords: Erythropoietin; NESP; Synthetic peptides; Polyclonal antibodies

Detection of manipulation in doping control urine sample collection: a multidisciplinary approach to determine identical urine samples by Mario Thevis; Hans Geyer; Ute Mareck; Gerd Sigmund; Jürgen Henke; Lotte Henke; Wilhelm Schänzer (pp. 1539-1543).

Manipulation of urine sampling in sports drug testing is considered a violation of anti-doping rules and is consequently sanctioned by regulatory authorities. In 2003, three identical urine specimens were provided by three different athletes, and the identity of all urine samples was detected and substantiated using numerous analytical strategies including gas chromatography–mass spectrometry with steroid and metabolite profiling, gas chromatography–nitrogen/phosphorus detector analysis, high-performance liquid chromatography–UV fingerprinting, and DNA-STR (short tandem repeat) analysis. None of the respective athletes was the donor of the urine provided for doping analysis, which proved to be a urine sample collected from other unidentified individual(s). Samples were considered suspicious based on identical steroid profiles, one of the most important parameters for specimen individualization in sports drug testing. A database containing 14,224 urinary steroid profiles of athletes was screened for specific values of 4 characteristic parameters (ratios of testosterone/epitestosterone, androsterone/etiocholanolone, androsterone/testosterone, and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol) and only the three suspicious samples matched all criteria. Further metabolite profiling regarding indicated medications and high-performance liquid chromatography–UV fingerprinting substantiated the assumption of manipulation. DNA-STR analyses unequivocally confirmed that the 3 urine samples were from the same individual and not from the athletes who provided DNA from either buccal cell material or blood specimens. This supportive evidence led to punishment of all three athletes according to the rules of the World Anti-Doping Agency. Application of a new multidisciplinary strategy employing common and new doping control assays enables the detection of urine substitution in sports drug testing. Figure Identical GC-MS/NPD profiles of three urine specimens collected from three different individuals for doping control purposes

Keywords: Doping; Manipulation; Mass spectrometry; Fingerprinting; DNA-STR; Individualization

Detection of diazepam in urine, hair and preserved oral fluid samples with LC-MS-MS after single and repeated administration of Myolastan® and Valium® by Marleen Laloup; Maria del Mar Ramirez Fernandez; Michelle Wood; Viviane Maes; Gert De Boeck; Yvan Vanbeckevoort; Nele Samyn (pp. 1545-1556).

Sedative agents are used to facilitate sexual assault due to their ability to render the victim passive, submissive and unable to resist. The primary pharmacological effect of the benzodiazepine tetrazepam is muscle relaxation, whereas the benzodiazepine diazepam acts on the central nervous system (CNS) exerting mainly sedation effects. Therefore, contrary to tetrazepam, diazepam is an often-abused drug, which can potentially be used as a date-rape drug. In this study, we describe the detection of low amounts of diazepam in Myolastan® (Sanofi–Synthelabo S.A., Brussels, Belgium) and Epsipam® (Will-Pharma, Wavre, Belgium) 50mg tablet preparations by LC-MS-MS, GC-FID and HPLC-DAD. Considering the important forensic implication of this finding, a study was conducted with volunteers receiving a single or repeated dosage of Myolastan®. Urine, hair and preserved oral fluid samples were analysed using a previously described sensitive and specific LC-MS-MS detection method allowing for the simultaneous quantification of tetrazepam, diazepam, nordiazepam, oxazepam and temazepam. This study demonstrates that diazepam can be observed in urine samples even after a single dose of Myolastan®. In addition, maintaining therapy for 1 week results in the detection of both diazepam and nordiazepam in urine samples and of diazepam in the first hair segment. Importantly, comparing urine and hair samples after a single intake of diazepam versus the single and 1 week administration of Myolastan® shows that the possible metabolic conversion of tetrazepam to diazepam is a more plausible explanation for the detection of diazepam in biological samples after the intake of Myolastan®. As such, these results reveal that the presence of diazepam and/or nordiazepam in biological samples from alleged drug-facilitated assault cases should be interpreted with care.

Keywords: LC-MS-MS; Tetrazepam; Diazepam; Urine; Hair; Oral fluid

Sections

Personal tools

Analytical and Bioanalytical Chemistry (v.388, #7)

Sections

Personal tools

Local resources

Analytical and Bioanalytical Chemistry (v.388, #7)