Insights into a TDM laboratory: daily routine or adventure?
| Autor: | G Zurek, N von Ahsen, Hartmut Kirchherr, WN Kühn-Velten |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Drug
Analyte Chromatography business.industry Metabolite media_common.quotation_subject Sample (material) General Medicine Pharmacology Triple quadrupole mass spectrometer Psychiatry and Mental health chemistry.chemical_compound chemistry Protein precipitation Medicine Pharmacology (medical) Sample preparation Dosing business media_common |
| Zdroj: | Pharmacopsychiatry. 47 |
| ISSN: | 1439-0795 0176-3679 |
| DOI: | 10.1055/s-0034-1386821 |
| Popis: | In order to flexibly address high throughput analysis for approx. 430 therapeutic drugs, the key requirements are skilled personnel, appropriate instrumentation including back-ups and minimal instrument downtime. Streamlined sample logistics using a barcode system guarantee minimal manual intervention including automated data transmission into the Laboratory Information Management System. Sample preparation by protein precipitation is fast and efficiently combined with LC-MS/MS analysis on six triple quadrupole systems. High throughput analysis (approx. 300 injections/night on one LC-MS/MS) is achieved by isocratic separations of 3 min to 5 min on one single chromatographic column. Maintaining a panel of several hundred analytes and integrating new drugs represents a challenge in itself. This is especially the case when a very sensitive analytical method for a potent drug is faced with difficult pre-analytical conditions such as specialized sampling, short half-life or instability (light, temperature). Novel potent drugs such as asenapine are analytically challenging due to the required sensitivity in the low µg/L-range to be achieved most desirably without any preconcentration in sample preparation. Agomelatine is an example for an antidepressant with a plasma half-life of 1 – 2h, and 80% of the metabolites are excreted in urine. Thus, the parent drug is rarely detected in a morning plasma sample after bed-time dosing. Positive findings were significantly increased in our laboratory (from 27.9% to 75.2%) by monitoring the hydroxylated metabolite released from its glucuronide after enzymatic hydrolysis. |
| Databáze: | OpenAIRE |
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