On-line desalting and determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in microdialysis and plasma samples using column switching and liquid chromatography/tandem mass spectrometry

Bengtsson, JörgenUppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Hammarlund-Udenaes (författare)

A sensitive and reproducible method for the determination of morphine and the metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was developed. The method was validated for perfusion fluid used in microdialysis as well as for sheep and human plasma. A C18 guard column was used to desalt the samples before analytical separation on a ZIC HILIC (hydrophilic interaction chromatography) column and detection with tandem mass spectrometry (MS/MS). The mobile phases were 0.05% trifluoroacetic acid (TFA) for desalting and acetonitrile/5 mM ammonium acetate (70:30) for separation. Microdialysis samples (5 microL) were directly injected onto the system. The lower limits of quantification (LLOQ) for morphine, M3G and M6G were 0.50, 0.22 and 0.55 ng/mL, respectively, and the method was linear from LLOQ to 200 ng/mL. For plasma, a volume of 100 microL was precipitated with acetonitrile containing internal standards (deuterated morphine and metabolites). The supernatant was evaporated and reconstituted in 0.05% TFA before the desalting process. The LLOQs for sheep plasma were 2.0 and 3.1 ng/mL and the ranges were 2.0-2000 and 3.1-3100 ng/mL for morphine and M3G, respectively. For human plasma, the LLOQs were 0.78, 1.49 and 0.53 ng/mL and the ranges were 0.78-500, 1.49-1000 and 0.53-500 ng/mL for morphine, M3G and M6G, respectively.

Jansson, BrittUppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Hammarlund-Udenaes(Swepub:uu)bja28141 (författare)
Hammarlund-Udenaes, MargaretaUppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Hammarlund-Udenaes(Swepub:uu)marghamm (författare)
Uppsala universitetAvdelningen för farmakokinetik och läkemedelsterapi (creator_code:org_t)

Ingår i:Rapid Communications in Mass Spectrometry: John Wiley & Sons19:15, s. 2116-21220951-41981097-0231

Av författaren/redakt...: Bengtsson, Jörge ...; Jansson, Britt; Hammarlund-Udena ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Farmaceutiska ve ...

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