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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ahsman, Maurice J. Van Der Nagel, Bart C. Mathot, Ron A. |
| Description | Country affiliation: Netherlands Author Affiliation: Ahsman MJ ( Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.) |
| Abstract | Currently, pharmacokinetic-pharmacodynamic studies of sedatives and analgesics are performed in neonates and children to find suitable dose regimens. As a result, sensitive assays using only small volumes of blood are necessary to determine drug and metabolite concentrations. We developed an ultra-performance liquid chromatographic method with tandem mass spectrometry detection for quantification of midazolam, 1-hydroxymidazolam, hydroxymidazolamglucuronide, morphine, morphine-3-glucuronide and morphine-6-glucuronide in 100 microL of plasma. Cleanup consisted of 96 wells micro-solid phase extraction, before reversed-phase chromatographic separation (ultra-performance liquid chromatography) and selective detection using electrospray ionization tandem mass spectrometry. Separate solid-phase extraction methods were necessary to quantify morphine, midazolam and their metabolites because of each group's physicochemical properties. Standard curves were linear over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 85-115% (of nominal concentration using a fresh calibration curve) and 15% (coefficient of variation, CV) respectively. Recoveries were >80% for all analytes, with interbatch CVs (as a measure of matrix effects) of less than 15% over six batches of plasma. Stability in plasma and extracts was sufficient, allowing large autosampler loads. Runtime was 3.00 min per sample for each method. The combination of 96-well micro-SPE and UPLC-MS/MS allows reliable quantification of morphine, midazolam and their major metabolites in 100 microL of plasma. |
| File Format | HTM / HTML |
| ISSN | 02693879 |
| Issue Number | 9 |
| Volume Number | 24 |
| e-ISSN | 10990801 |
| Journal | Biomedical Chromatography |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2010-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Discipline Molecular Biology Discipline Biochemistry Discipline Pharmacology Chromatography, High Pressure Liquid Methods Midazolam Blood Morphine Solid Phase Extraction Tandem Mass Spectrometry Humans Molecular Structure Spectrometry, Mass, Electrospray Ionization Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Analytical Chemistry Drug Discovery Clinical Biochemistry Biochemistry Molecular Biology Pharmacology |
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