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  • 1
    Online Resource
    Online Resource
    Conductive vial electromembrane extraction of opioids from oral fluid
    Springer Science and Business Media LLC ; 2023
    In:  Analytical and Bioanalytical Chemistry Vol. 415, No. 22 ( 2023-09), p. 5323-5335
    Details
    In: Analytical and Bioanalytical Chemistry, Springer Science and Business Media LLC, Vol. 415, No. 22 ( 2023-09), p. 5323-5335
    Abstract: The use of oral fluid as sample matrix has gained significance in the analysis of drugs of abuse due to its non-invasive nature. In this study, the 13 opioids morphine, oxycodone, codeine, O-desmethyl tramadol, ethylmorphine, tramadol, pethidine, ketobemidone, buprenorphine, fentanyl, cyclopropylfentanyl, etonitazepyne, and methadone were extracted from oral fluid using electromembrane extraction based on conductive vials prior to analysis with ultra-high performance liquid chromatography–tandem mass spectrometry. Oral fluid was collected using Quantisal collection kits. By applying voltage, target analytes were extracted from oral fluid samples diluted with 0.1% formic acid, across a liquid membrane and into a 300 μL 0.1% (v/v) formic acid solution. The liquid membrane comprised 8 μL membrane solvent immobilized in the pores of a flat porous polypropylene membrane. The membrane solvent was a mixture of 6-methylcoumarin, thymol, and 2-nitrophenyloctyl ether. The composition of the membrane solvent was found to be the most important parameter to achieve simultaneous extraction of all target opioids, which had predicted log P values in the range from 0.7 to 5.0. The method was validated in accordance to the guidelines by the European Medical Agency with satisfactory results. Intra- and inter-day precision and bias were within guideline limits of ± 15% for 12 of 13 compounds. Extraction recoveries ranged from 39 to 104% (CV ≤ 23%). Internal standard normalized matrix effects were in the range from 88 to 103% (CV ≤ 5%). Quantitative results of authentic oral fluid samples were in accordance with a routine screening method, and external quality control samples for both hydrophilic and lipophilic compounds were within acceptable limits.
    Type of Medium: Online Resource
    ISSN: 1618-2642 , 1618-2650
    URL: Article
    DOI: 10.1007/s00216-023-04807-3
    RVK:
    VA 4300
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1459122-4
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    SSG: 12
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  • 2
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    Online Resource
    Quantitative determination of R/S‐methadone in human serum using ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry: A method for routine use
    Wiley ; 2024
    In:  Drug Testing and Analysis
    Details
    In: Drug Testing and Analysis, Wiley
    Abstract: Methadone has two enantiomers, which exhibit differences in pharmacological effects, with R‐methadone being the active and S‐methadone the inactive enantiomer. A robust, simple and rapid method for chiral separation of the two enantiomers in serum samples using ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry (UHPSFC‐MSMS) has been developed and validated. Enantiomeric separation was achieved using a Chiralpak IH‐3 column with a mobile phase consisting of CO 2 and 30mM ammonium acetate in methanol/water (98/2, v/v). Runtime was 4 minutes. Sample preparation was semi‐automated using a Hamilton ML Star robot with protein precipitation, and phospholipid removal was carried out using a Waters OSTRO™ 96‐well plate. The calibration range was 50.0–1,500 nM for each enantiomer. The between‐assay relative standard deviations were in the range of 1.2–3.6%. Matrix effects ranged from 99% to 115% corrected with internal standard. The method has been implemented in our laboratory and has proven to be a robust and reliable method for determining the ratio of R/S‐methadone in authentic patient samples.
    Type of Medium: Online Resource
    ISSN: 1942-7603 , 1942-7611
    URL: Article
    DOI: 10.1002/dta.3693
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2462344-1
    SSG: 15,3
    SSG: 31
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  • 3
    Online Resource
    Online Resource
    Determination of psychoactive drugs in serum using conductive vial electromembrane extraction combined with UHPLC-MS/MS
    Elsevier BV ; 2021
    In:  Journal of Chromatography B Vol. 1183 ( 2021-10), p. 122926-
    Details
    In: Journal of Chromatography B, Elsevier BV, Vol. 1183 ( 2021-10), p. 122926-
    Type of Medium: Online Resource
    ISSN: 1570-0232
    URL: Article
    DOI: 10.1016/j.jchromb.2021.122926
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1491259-4
    SSG: 11
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  • 4
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    Stability of 21 Antihypertensive Drugs in Serum Collected in Standard (Nongel) Serum Tubes Versus Tubes Containing a Gel Separator
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Therapeutic Drug Monitoring Vol. 42, No. 2 ( 2020-04), p. 335-340
    Details
    In: Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 2 ( 2020-04), p. 335-340
    Abstract: Therapeutic drug monitoring of antihypertensive drugs is being increasingly used to optimize treatment and to assess nonadherence. Separator gels are often used in blood collection tubes to facilitate serum or plasma separation from other blood constituents before analyses. Drug adsorption into the separator gel presents a possible pre-analytical cause of falsely low concentrations or false negative results. Methods: Drug-free blood from blood donors was spiked with therapeutic concentrations of 21 antihypertensive drugs, transferred to serum tubes with and without separator gel (Vacuette gel plastic tubes and plain serum plastic tubes, respectively), and centrifuged. Serum was collected immediately after centrifugation and after 24 and 72 hours of room temperature storage, samples were analyzed in triplicates using liquid chromatography–mass spectrometry. Results: Serum samples collected immediately after centrifugation or 24 hours later, had the same drug concentrations in the gel and nongel tubes. After 72 hours of room temperature storage, verapamil and lercanidipine serum concentrations were 43% and 29%, respectively, lower in gel tubes than nongel tubes. Canrenone, diltiazem, and bendroflumethiazide showed between 10% and 20% concentration loss in gel tubes, compared with nongel tubes, with the 2 latter observed as unstable also in nongel tubes. Conclusions: Except for verapamil, lercanidipine, and canrenone, which showed substantial concentration loss in gel tubes, gel tubes may be used for therapeutic drug monitoring purposes for the most commonly used antihypertensive drugs. Transferring serum to gel-free containers immediately after centrifugation minimizes concentration loss; however, bendroflumethiazide and diltiazem are generally unstable at room temperature.
    Type of Medium: Online Resource
    ISSN: 0163-4356
    URL: Article
    DOI: 10.1097/FTD.0000000000000708
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2048919-5
    SSG: 15,3
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  • 5
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    Stability of Direct Oral Anticoagulants and Antiarrhythmic Drugs in Serum Collected in Standard (Nongel) Serum Tubes Versus Tubes Containing Gel Separators
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Therapeutic Drug Monitoring Vol. 44, No. 2 ( 2022-04), p. 328-334
    Details
    In: Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 2 ( 2022-04), p. 328-334
    Abstract: Separation gels are often used in collection tubes, but adsorption of drugs onto the gel may cause falsely low concentrations in therapeutic drug monitoring. In this study, the stability of apixaban, edoxaban, rivaroxaban, flecainide, amiodarone, and desethylamiodarone was assessed in tubes, with and without gel separators. Methods: Drug-free blood was spiked and stored for up to 7 days in nongel tubes and gel tubes from 2 manufacturers (Vacuette and Vacutainer). The samples were analyzed in triplicates using ultra-high-pressure liquid chromatography–tandem mass spectrometry. Results: At ambient temperature conditions, the serum concentrations of apixaban, edoxaban, and rivaroxaban in a tube with acrylic-based gel had already decreased at baseline, whereas it took 6 hours to observe the same result in a tube with olefin-based gel. At 4°C, the reduction in serum concentration was considerably slower. For flecainide, the gel tube concentrations were stable at ambient temperature for 3 days, but decreased after 7 days in acrylic-based gel tubes. Amiodarone and desethylamiodarone stored in gel tubes at 4°C showed decrease in concentrations after 24 hours and 6 hours, respectively. Conclusions: Acrylic-based gel tubes should not be used for any of the tested drugs. Although olefin-based gel tubes may be used for anticoagulants and flecainide, it is advisable to prefer nongel tubes as a general precaution.
    Type of Medium: Online Resource
    ISSN: 0163-4356
    URL: Article
    DOI: 10.1097/FTD.0000000000000915
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2048919-5
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  • 6
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    Enantiomeric separation and quantification of R/S‐amphetamine in serum using semi‐automated liquid‐liquid extraction and ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry
    Wiley ; 2020
    In:  Drug Testing and Analysis Vol. 12, No. 9 ( 2020-09), p. 1344-1353
    Details
    In: Drug Testing and Analysis, Wiley, Vol. 12, No. 9 ( 2020-09), p. 1344-1353
    Abstract: The amphetamine molecule contains a chiral center and its enantiomers exhibit differences in pharmacological effects, with the S‐enantiomer mediating most of the central nervous system stimulating activity. The majority of prescribed amphetamine consists of the pure S‐enantiomer, but therapeutic formulations containing the R‐enantiomer in various proportions are also available. Illegal amphetamine remains available mainly as a racemic mixture of the R‐ and S‐enantiomers. To distinguish between legal and illegal consumption of amphetamine a method for enantiomeric separation and quantification of R/S‐amphetamine in serum was developed and validated using ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry (UHPSFC‐MS/MS). Sample preparation prior to UHPSFC‐MS/MS analysis was performed by a semi‐automated liquid–liquid extraction method. The UHPSFC‐MS/MS method used a Chiralpak AD‐3 column with a mobile phase consisting of CO 2 and 0.1% ammonium hydroxide in 2‐propanol/methanol (50/50, v/v). The injection volume was 2 μL and run time was 4 minutes. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions ( m/z 136.1 〉 119.0 and m/z 136.1 〉 91.0). The calibration range was 12.5–1,000 nM for each analyte. The between‐assay relative standard deviations were in the range of 1.3–3.0%. Recovery was 73% and matrix effects ranged from 95 to 100% when corrected with internal standard. After development and validation, the method has been successfully implemented in our laboratory for both separation and quantification of R/S‐amphetamine and has proved to be a reliable and useful tool for distinguishing intake of R‐ and S‐amphetamine in authentic patient samples.
    Type of Medium: Online Resource
    ISSN: 1942-7603 , 1942-7611
    URL: Issue
    URL: Article
    DOI: 10.1002/dta.v12.9
    DOI: 10.1002/dta.2879
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2462344-1
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  • 7
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    Online Resource
    Determination of amphetamine enantiomers in urine by conductive vial electromembrane extraction and ultra‐high performance supercritical fluid chromatography tandem mass spectrometry
    Wiley ; 2023
    In:  Drug Testing and Analysis Vol. 15, No. 8 ( 2023-08), p. 909-918
    Details
    In: Drug Testing and Analysis, Wiley, Vol. 15, No. 8 ( 2023-08), p. 909-918
    Abstract: Separation and quantification of amphetamine enantiomers are commonly used to distinguish between consumption of prescription amphetamine (mostly S ‐amphetamine) and illicit forms of the drug (racemate). In this study, electromembrane extraction with prototype conductive vials was combined with ultra‐high performance supercritical fluid chromatography (UHPSFC‐MS/MS) to quantify R ‐ and S ‐amphetamine in urine. Amphetamine was extracted from 100 μL urine, diluted with 25 μL internal standard solution and 175 μL 130 mM formic acid, across a supported liquid membrane (SLM) consisting of 9 μL of a 1:1(w/w) mixture of 2‐nitrophenyloctyl ether (NPOE) and bis(2‐ethylhexyl)phosphite (DEHPi) into an acceptor phase containing 300 μL 130 mM formic acid. The extraction was facilitated by the application of 30 V for 15 min. Enantiomeric separation was achieved using UHPSFC‐MS/MS with a chiral stationary phase. The calibration range was 50–10,000 ng/mL for each enantiomer. The between‐assay CV was ≤5%, within‐assay CV ≤ 1.5%, and bias within ±2%. Recoveries were 83%–90% (CV ≤ 6%), and internal standard corrected matrix effects were 99–105 (CV ≤ 2%). The matrix effects ranged from 96% to 98% (CV ≤ 8%) when not corrected by the internal standard. The EME method was compared with a chiral routine method that employed liquid–liquid extraction (LLE) for sample preparation. Assay results were in agreement with the routine method, and the mean deviation between methods was 3%, ranging from −21% to 31%. Finally, sample preparation greenness was assessed using the AGREEprep tool, which resulted in a greenness score of 0.54 for conductive vial EME, opposed to 0.47 for semi‐automated 96‐well LLE.
    Type of Medium: Online Resource
    ISSN: 1942-7603 , 1942-7611
    URL: Issue
    URL: Article
    DOI: 10.1002/dta.v15.8
    DOI: 10.1002/dta.3487
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2462344-1
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    SSG: 31
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  • 8
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    Online Resource
    Association between low body weight and cytochrome P‐450 enzyme activity in patients with anorexia nervosa
    Wiley ; 2020
    In:  Pharmacology Research & Perspectives Vol. 8, No. 3 ( 2020-06)
    Details
    In: Pharmacology Research & Perspectives, Wiley, Vol. 8, No. 3 ( 2020-06)
    Abstract: Very little is known to which extent severe underweight could affect cytochrome P‐450 (CYP) enzyme activity. In this study, 24 patients with anorexia nervosa at two occasions ingested single oral doses of five test drugs known to be metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. A mixed model analysis was used to evaluate the effect of changes in body mass index (BMI) on the metabolic activities of these enzymes. The primary end point was the change in drug/metabolite ratio of each of the test drugs per kg/m 2 change in BMI. With increasing BMI, the metabolic activity of CYP3A4 decreased (change in the CYP3A4 drug/metabolite ratio per unit change in BMI = 0.056; 95% confidence interval [CI] 0.011 to 0.102; P  = .017). For CYP1A2, increasing BMI increased the metabolic activity with borderline significance (change in the CYP1A2 drug/metabolite ratio per unit change in BMI = –0.107; CI –0.220 to 0.005; P  = .059). For CYP2C9, CYP2C19, and CYP2D6, no significant changes were seen. The clinical impact of these findings for drug treatment in patients with anorexia nervosa and other severely underweight patients needs to be further studied by examining the pharmacokinetics of specific drugs. This might be particularly relevant for drugs metabolized by CYP1A2 and/or CYP3A4.
    Type of Medium: Online Resource
    ISSN: 2052-1707 , 2052-1707
    URL: Issue
    URL: Article
    DOI: 10.1002/prp2.v8.3
    DOI: 10.1002/prp2.615
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2740389-0
    SSG: 15,3
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  • 9
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    Online Resource
    Serum or Plasma for Quantification of Direct Oral Anticoagulants?
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Therapeutic Drug Monitoring Vol. 44, No. 4 ( 2022-08), p. 578-584
    Details
    In: Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 4 ( 2022-08), p. 578-584
    Abstract: Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements. Methods: Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity. Results: Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P 〈 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivaroxaban (both P 〈 0.001). Factor X antigen measurements in citrate-plasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma. Conclusions: Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.
    Type of Medium: Online Resource
    ISSN: 0163-4356
    URL: Article
    DOI: 10.1097/FTD.0000000000000956
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2048919-5
    SSG: 15,3
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