Basic drug analysis by strong cation-exchange liquid chromatography-tandem mass spectrometry: simultaneous analysis of amisulpride, and of metamfetamine and amfetamine in serum/plasma.
In the HPLC of basic drugs and metabolites, good efficiency and peak shape can often be attained using strong cation-exchange packings with isocratic 100% methanol eluents containing an ionic modifier at an appropriate pH* and ionic strength. Solvent extracts can be analysed directly, and use of ammonium acetate as modifier facilitates the use of atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry, selected reaction monitoring mode. For the analysis of amisulpride and of metamfetamine/amfetamine in plasma (200 µL) after single oral doses in man, a column packed with Waters Spherisorb S5SCX (5 µm average particle size, 100 × 2.1 mm i.d.) was used with methanolic ammonium acetate (40 mmol/L, pH* 6.0, flow rate 0.5 mL/min) as eluent (35°C). Deuterated internal standards were used for each analyte. Detection was by positive-mode APCI. Responses for all analytes were linear over the calibration ranges. Intra-assay precision (RSD) was 2-18%, and inter-assay precision was 2-12%. The limit of detection was 0.5 µg/L for all analytes. No significant matrix effects or isobaric interferences were noted. The total analysis time was 7 min. Similar methodology can be applied to a wide range of basic analytes using MS/MS detection.
Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK. lewis.couchman@nhs.net
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L
Couchman
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Morgan
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RJ
Flanagan
D000077582:Amisulpride; D000661:Amphetamine / Q000097:blood*; D002412:Cations; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D008694:Methamphetamine / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002412:Cations; D008694:Methamphetamine; D013469:Sulpiride; D000077582:Amisulpride; D000661:Amphetamine