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1.
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. 相似文献
2.
Liquid chromatography coupled to mass spectrometry nowadays plays an important role in the field of therapeutic drug monitoring
(TDM), especially of new compounds for which no immunoassays are available. This paper reviews LC–MS(–MS) methods published
recently for anti-infective drugs: antiretroviral drugs, other antiviral drugs, antibacterial drugs, antihelmintic drugs,
antimalarial drugs, and other antiprotozoal drugs. An overview of the different methods is given, with special focus on selection
of the internal standard and validation procedures. 相似文献
3.
B. Avula L. M. Tripathi S. I. Khan B. L. Tekwani D. Nanayakkara W. Gul M. A. ElSohly I. A. Khan 《Chromatographia》2006,64(7-8):429-434
NPC1161 is an 8-aminoquinoline anti-malarial analog, which has a favorable toxicity profile relative to primaquine and other 8-aminoquinolines. High-performance liquid chromatographic method was developed for the determination of NPC1161, primaquine and their metabolites in biological samples in order to facilitate metabolic and pharmacokinetic studies. The method includes extraction of the unchanged drugs and their metabolites from the biological samples. Separation was achieved by reversed-phase chromatography on a C18 column with water–acetonitrile both containing 0.025% trifluoroacetic acid as the mobile phase. Recoveries of NPC1161 and its metabolites were greater than 60% in various biological samples tested. No interference with the components of the biological material was observed. The detector response was linear with concentrations of NPC1161 and its metabolites (desalkyl NPC1161 and carboxy NPC1161) in the ranges from 0.5 to 80.0, 0.4–60.0 and 0.4–70.0 μg mL−1, respectively. A mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification of NPC1161 and its metabolites in biological samples. This method involved the use of the [M + H]+ions of NPC1161, C3 analog (internal std. for the assay), desalkyl NPC1161 and carboxy NPC1161 at m/z 434, 406, 349 and 449 in the positive ion mode with extractive ion monitoring (EIM). This method will have an important application in pharmacokinetic studies of NPC1161 and in understanding the mechanism of metabolism of this novel 8-aminoquinoline analog in more detail. 相似文献
4.
Current role of LC–MS(/MS) in doping control 总被引:1,自引:0,他引:1
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. 相似文献
5.
Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are
abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical
and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists.
Combined chromatography–mass spectrometry techniques with standardised reference libraries have been most commonly used for
the purpose. In the last ten years, the focus has shifted from gas chromatography–mass spectrometry to liquid chromatography–mass
spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new
relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power,
has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation.
The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both
techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound’s or a fragment’s
mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic
pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution
is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review
discusses recent applications of HRMS in analytical toxicology. 相似文献
6.
Johanna Ristimaa Merja Gergov Anna Pelander Erja Halmesmäki Ilkka Ojanperä 《Analytical and bioanalytical chemistry》2010,398(2):925-935
Analysis of the major drugs of abuse in meconium has been established in clinical practice for detecting fetal exposure to
illicit drugs, particularly for the ready availability of the sample and ease of collection from diapers, compared with neonatal
hair and urine. Very little is known about the occurrence and detection possibilities of therapeutic and licit drugs in meconium.
Meconium specimens (n = 209) were collected in delivery hospitals, from infants of mothers who were suspected to be drug abusers. A targeted analysis
method by liquid chromatography–triple quadrupole mass spectrometry (LC-MS/MS) was developed for abused drugs: amphetamine,
methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, morphine, codeine, 6-monoacetylmorphine,
oxycodone, methadone, tramadol, buprenorphine, and norbuprenorphine. A separate LC-MS/MS method was developed for 11-nor-∆9-tetrahydrocannabinol-9-carboxylic acid. A screening method based on LC coupled to time-of-flight MS was applied to a broad
spectrum of drugs. As a result, a total of 77 different compounds were found. The main drug findings in meconium were as follows:
local anesthetics 82.5% (n = 172), nicotine or its metabolites 61.5% (n = 129), opioids 48.5% (n = 101), stimulants 21.0% (n = 44), hypnotics and sedatives 19.0% (n = 40), antidepressants 18.0% (n = 38), antipsychotics 5.5% (n = 11), and cannabis 3.0% (n = 5). By revealing drugs and metabolites beyond the ordinary scope, the present procedure helps the pediatrician in cases
where maternal denial is strong but the infant seems to suffer from typical drug-withdrawal symptoms. Intrapartum drug administration
cannot be differentiated from gestational drug use by meconium analysis, which affects the interpretation of oxycodone, tramadol,
fentanyl, pethidine, and ephedrine findings. 相似文献
7.
Cao YG Zhang M Yu D Shao JP Chen YC Liu XQ 《Analytical and bioanalytical chemistry》2008,391(3):1063-1071
An advanced quantification method was developed with solid-phase extraction (SPE) and mass spectrometry (MS) determination
for nafamostat, an unstable and highly polar drug, in human plasma. For unstable drugs with an ester group, the main analytical
challenge is how to avoid the ester hydrolysis, and strong acid or alkaline conditions should be excluded during sample preparation.
Considering that, we developed a relatively mild method with SPE for sample preparation without strong acid and alkaline treatment,
which was optimized with different pHs and salt concentrations in phosphate-buffered saline treatment. The results indicated
that pH 5 gave the most efficient extraction and 0.1 M salt concentration enhanced the extraction the most, with a minor effect
on MS monitoring. The extraction method effectively avoided drug hydrolysis and achieved good drug enrichment over 82.2%.
The linear range of quantification was 1.25–160 ng mL−1. The stability of the drug in sample treatment was fully validated according to the sample processing procedure, including
the stability in fresh blood, mobile phase, plasma and acidic methanol, and the results indicated that the drug remained stable
during the whole sample preparation. Compared with a previous isotope-labeling method, more accurate and specific quantification
of plasma concentration was achieved with liquid chromatography–electrospray ionization MS determination. With use of our
method, nafamostat mesilate pharmacokinetics in 30 Chinese healthy volunteers was investigated with three doses via intravenous-drip
infusion. The pharmacokinetic parameters were also estimated and compared with those of Japanese volunteers (slightly lower
plasma concentration and longer terminal elimination half-life for Chinese volunteers). The difference in the pharmacokinetics
may be ascribed to the quantification method, because previous isotope labeling may have overestimated the parent drug. 相似文献
8.
Kintz P 《Analytical and bioanalytical chemistry》2007,388(7):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. 相似文献
9.
Thorsteinn Loftsson Fífa Konrádsdóttir Már Másson 《Journal of inclusion phenomena and macrocyclic chemistry》2007,57(1-4):613-617
Most drugs permeate biological membranes via passive diffusion and it is generally assumed that the main barrier is the lipophilic
structure of the membranes. However, it has been observed that an unstirred water layer adjacent to the membrane surface can
in some cases be just as effective barrier as the lipophilic membrane itself. Hydrophilic cyclodextrins can enhance drug delivery
through biological membranes by increasing the availability of dissolved drug molecules immediate to the membrane surface,
i.e., by increasing drug delivery through the unstirred water layer. We have developed an artificial octanol membrane that
is cheap and simple to prepare. The novel membrane consists of a hydrated semi-permeable cellophane membrane with a molecular
weight cut off (MWCO) of 12,000–14,000 that mimics the unstirred water layer and a lipophilic membrane of pure n-octanol in a nitrocellulose matrix. The membrane was used to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HPβCD)
on the flux of hydrocortisone through the membrane. In aqueous HPβCD saturated with hydrocortisone the drug concentration
gradient, over the unstirred water layer, increased with increasing HPβCD concentration which resulted in enhanced drug delivery
through the membrane. When excess HPβCD was present in the donor phase the octanol/water partition coefficient decreased with
increasing HPβCD concentration that lead to decreased drug delivery through the membrane. 相似文献
10.
Liquid chromatography–(tandem) mass spectrometry [(LC-MS(/MS)] has become an integral part of modern sports drug testing as
it offers unique capabilities complementing immunological and gas chromatography–(tandem) mass spectrometry [(GC-MS(/MS)]-based
detection methods for prohibited compounds. The improved options of fast and sensitive targeted analysis as well as untargeted
screening procedures utilizing high resolution/high accuracy mass spectrometry have considerably expanded the tools available
to anti-doping laboratories for initial testing and confirmation methods. One approach is to focus on pre-selected target
analytes that are measured with utmost specificity and sensitivity using diagnostic precursor–product ion pairs in low resolution
tandem mass spectrometers. The other scenario is to measure and plot extracted ion chromatograms of protonated or deprotonated
molecules as well as product ions as recorded in the full scan mode with high resolution/high accuracy mass spectrometry.
Examples of recent applications of sports drug testing procedures published between 2007 and 2010 are presented and discussed,
outlining the particular advantages of the selected approaches as well as their limitations in a short- and long-term perspective. 相似文献
11.
Gjelstad A Rasmussen KE Pedersen-Bjergaard S 《Analytical and bioanalytical chemistry》2009,393(3):921-928
The present work describes the first systematic study of electromembrane extraction (EME) from biological matrices under physiological
conditions. Six basic drugs with protein binding in the range of 20–97% were extracted from untreated human plasma and whole
blood through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene impregnated in the walls of a hollow
fiber, and into an acidified aqueous solution inside the lumen of the fiber. The electrical potential difference over the
membrane reduced the protein binding of the drugs and transported the free drug fraction over the membrane. Recoveries in
the range 25–65% were obtained with 10-min extraction time and an applied voltage of only 10 V over the SLM. Interday precision
better than 20% RSD and linearity in the range 0.5–10 μg/mL were obtained for nortriptyline and methadone. Extraction from
untreated whole blood was also demonstrated with recoveries in the range 19–51%. 相似文献
12.
Kolocouri F Dotsikas Y Apostolou C Kousoulos C Loukas YL 《Analytical and bioanalytical chemistry》2007,387(2):593-601
An automated, sensitive and high-throughput liquid chromatographic/electrospray tandem mass spectrometric (LC–MS/MS) assay
was developed for the simultaneous determination of losartan (LOS), its major circulating metabolite EXP-3174 and hydrochlorothiazide
(HCTZ) in human plasma. LOS and HCTZ coexist in the same drug formulation, and this is the first method that enables the simultaneous
determination of both drugs along with the active metabolite of LOS. Since these drugs have different physicochemical properties,
the employment of a liquid–liquid extraction (LLE) protocol was precluded. A fully automated solid-phase extraction (SPE)
protocol, based on 96-well format plates, was used to isolate these compounds and furosemide (internal standard, IS) from
plasma. Washing and elution steps were amended accordingly in order to minimize any matrix effect from components of the plasma
without reducing the elution of the molecules of interest. The compounds were eluted from a C18 column and detected with an
API 3000 triple-quadrupole mass spectrometer using negative electrospray ionization and multiple reaction monitoring (MRM).
The assay was linear over the range 1.00–400 ng/mL for LOS and EXP-3174 and 0.500–200 ng/mL for HCTZ, respectively, when 200 μl
of plasma was used in the extraction. The overall intra- and interassay variations were within acceptance limits. The analysis
time for each sample was 4 min, and more than 300 samples could be analyzed in one day by running the system overnight. The
assay was simple, highly sensitive, selective, precise, fast, and it enables the reliable determination of LOS, EXP-3174 and
HCTZ in pharmacokinetic or bioequivalence studies after per os administration of a single tablet containing both drugs. 相似文献
13.
The role of alternative specimens in toxicological analysis 总被引:1,自引:0,他引:1
The use of alternative specimens in the field of toxicology was first described in 1979, when hair analysis was used to document chronic drug exposure. Since then, the use of these 'alternative' samples has gained tremendous importance in forensic toxicology, as well as in clinic toxicology, doping control and workplace drug testing. It is not surprising, therefore, that a large number of papers dealing with the determination of several classes of drugs in saliva, sweat, meconium and hair have been published ever since, owing to the fact that chromatographic equipment is becoming more and more sensitive, mass spectrometry (and tandem mass spectrometry) being the most widely used analytical tool, combined with gas or liquid chromatography. 'Alternative' specimens present a number of advantages over the 'traditional' samples normally used in toxicology (e.g. blood, urine and tissues), namely the fact that their collection is not invasive, their adulteration is difficult, and they may allow increased windows of detection for certain drugs. The main disadvantage of this kind of samples is that drugs are present in very low concentrations, and therefore high-sensitivity techniques are required to accomplish the analysis. This paper reviews a series of publications on the use of alternative specimens, with special focus on the main analytical and chromatographic problems that these samples present, as well on their advantages and disadvantages over traditional samples in documenting drug exposure. 相似文献
14.
Skalka N Krol A Schlesinger H Altstein M 《Analytical and bioanalytical chemistry》2011,400(10):3491-3504
The present research focused on the development of an immunoassay and an immunochemical sol–gel-based immunoaffinity purification
(IAP) method for purification and detection of the non-steroid anti-inflammatory drug (NSAID) indomethacin (IMT). A polyclonal
antibody (Ab) for IMT was generated, and two sensitive microplate assays for the detection of IMT were developed (termed OV
and HRP formats), based on the enzyme-linked immunosorbent assay (ELISA) method. The limits of detection of the assays were
15 ± 1.25 ng mL−1 (n = 50) and 12 ± 0.17 ng mL−1 (n = 4) for the OVA and HRP formats, respectively. The Abs exhibited slight cross-reactivity with other NSAIDs. The Abs were
also used to develop a sol–gel-based IAP method for clean-up and concentration of IMT. Several sol–gel formats with various
amounts of antibodies were examined; the best and most reproducible format was at a TMOS:HCl molar ratio of 1:6 in which 120 μL
of IMT Abs was entrapped. The binding capacity under these conditions was ca. 100 to 250 ng of IMT with very low non-specific
binding (less than 5% of the applied amount). The sol–gel IAP method, combined with solid-phase extraction, successfully eliminated
serum interference to a degree that enabled analysis of spiked serum samples by ELISA. The method was also found to be fully
compatible with subsequent chemical analytical methods, such as liquid chromatography followed by mass spectrometry. The approaches
developed in this study form a basis for analysis of IMT in biological samples in order to monitor their pharmacokinetic properties,
and may be further used to study population exposure to IMT, and to monitor the occurrence of IMT contamination in water samples. 相似文献
15.
Ardjomand-Woelkart K Kollroser M Li L Derendorf H Butterweck V Bauer R 《Analytical and bioanalytical chemistry》2011,400(8):2371-2381
A rapid and selective high-throughput HESI-LC-MS/MS method for determining eight cytochrome P450 probe drugs in one-step extraction
and single run was developed and validated. The four specific probe substrates midazolam, dextromethorphan, tolbutamide, theophylline
and their metabolites 1-hydroxymidazolam, dextrorphan, hydroxyl(methyl)tolbutamide, 1,3-dimethyluric acid, together with the
deuterated internal standards, were extracted from rat plasma using a novel 96-well Hybrid-SPE™-precipitation technique. The
bioanalytical assay was based on reversed phase liquid chromatography coupled with tandem mass spectrometry in the positive
ion mode using selected reaction monitoring for drug (-metabolite) quantification. All analytes were separated simultaneously
in a single run that lasted less than 11 min. The intra- and inter-day precisions for all eight substrates/metabolites were
1.62–12.81% and 2.09–13.02%, respectively, and the relative errors (accuracy) for the eight compounds ranged from −9.62% to
7.48% and −13.84% to 8.82%. Hence, the present method provides a robust, fast and reproducible analytical tool for the evaluation
of four major drug metabolising cytochrome P450 (3A4, 2C9, 1A2 and 2D6) activities with a cocktail approach in rats to clarify
herb–drug interactions. The method can be used as a basic common validated high-throughput analytical assay for in vivo interaction
studies. 相似文献
16.
17.
Ana Fortuna Joana Sousa Gilberto Alves Amílcar Falcão Patrício Soares-da-Silva 《Analytical and bioanalytical chemistry》2010,397(4):1605-1615
For the first time, a simple, selective and accurate high-performance liquid chromatography method with ultraviolet detection
was developed and validated to quantify simultaneously three structurally related antiepileptic drugs; carbamazepine, oxcarbazepine,
and the recently launched eslicarbazepine acetate and their main metabolites, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and licarbazepine. The method involves a solid-phase extraction and a reverse-phase
C18 column with 5 cm length. The mobile phase consisting of water, methanol, and acetonitrile in the ratio 64:30:6 was selected
as the best one and pumped at 1 mL/min at 40 °C. The use of this recent column and an aqueous mobile phase instead of buffers
gives several advantages over the method herein developed; namely the fact that the chromatographic analysis takes only 9 min.
The method was validated according to the guidelines of the Food and Drug Administration, showing to be accurate (bias within
±12%), precise (coefficient variation <9%), selective and linear (r
2 > 0.997) over the concentration range of 0.05–30 μg/mL for carbamazepine; 0.05–20 μg/mL for oxcarbazepine; 0.15–4 μg/mL for
eslicarbazepine acetate; 0.1–30 μg/mL for carbamazepine-10,11-epoxide; 0.1–10 μg/mL for 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and 0.1–60 μg/mL for licarbazepine. It was also shown that this method can adequately
be used for the therapeutic drug monitoring of the considered antiepileptic drugs, carbamazepine, oxcarbazepine, eslicarazepine
acetate, and their metabolites. 相似文献
18.
Meermann B Bockx M Laenen A Van Looveren C Cuyckens F Vanhaecke F 《Analytical and bioanalytical chemistry》2012,402(1):439-448
The aim of this work was speciation analysis of metabolites in feces samples collected within a clinical study during which
a bromine-containing anti-tuberculosis drug (TMC207) was administered to patients with multi-drug resistant tuberculosis infection.
Owing to slow elimination of the drug, no 14C label was used within this study. Quantification of the bromine species was accomplished using high performance liquid chromatography
coupled to inductively coupled plasma–mass spectrometry (HPLC/ICP-MS) in combination with on-line isotope dilution (on-line
ID), while structural elucidation of the species was performed using HPLC coupled to electrospray ionization–mass spectrometry.
The ICP-MS-based method developed shows a good intra- and inter-day reproducibility (relative standard deviation = 3.5%, N = 9); the limit of detection (1.5 mg TMC207 L−1) is of the same order of magnitude as that for HPLC/radiodetection; the dynamic range of the method covers more than two
orders of magnitude. Furthermore, the column recovery was demonstrated to be quantitative (recoveries between 90.6% and 99.5%).
Based on the excellent figures of merit, the “cold” HPLC/ICP-MS approach could be deployed for the actual human in vivo metabolism study, such that exposure of the human volunteers to the 14C radiolabel was avoided. 相似文献
19.
20.
Residual antimicrobials in food constitute a risk to human health. Although epidemiological data on the real magnitude of
their adverse effects are very scarce, they indicate that food could be an important vehicle for evolution and dissemination
of antimicrobial-resistant bacteria. Public health agencies in many countries rely on detection by mass spectrometry (MS)
for unambiguous identification of residues of antimicrobial agents in animal food products for human consumption. The introduction
of relatively inexpensive and robust liquid chromatography (LC)–MS systems has given a strong impulse to the development of
confirmatory methods for the above medicines in foodstuffs. The initial part of this review, after a brief introduction into
the field of antimicrobials, is dedicated to the most important EU regulations and directives for control of residues of these
substances in animal products. The main attention in this review is on the sample-treatment and MS detection systems in use
today for analysing the most important classes of antimicrobials in various biological matrices (milk, animal tissues, eggs,
and honey). As evidenced by this review, reversed-phase LC combined with tandem MS, usually triple-quadrupole MS (QqQMS),
is currently the preferred technique in most residue analysis of a single-class of antimicrobials. A recently emerging analytical
strategy is that of developing methods for detecting a large variety of veterinary drugs belonging to different classes, including
pesticides (multi-class residue analysis). To do this, simple and generic extraction and separation techniques applicable
to a broad range of compounds differing in physical and chemical properties have been adopted. Such methods are still based
mainly on LC–QqQMS. Emerging alternative MS detection systems are time-of-flight MS, which provides accurate mass of the analyte(s),
or Q–linear ion trap (IT) MS that eliminates some limitations of ITMS
n
. 相似文献