TY - JOUR

T1 - An Advanced Double Column-Switching Technique (LC-LC) for Liquid Chromatography/Electrospray Ionisation Tandem Mass Spectrometry for Fully Automated Analysis of Caspofungin

AU - Egle, Hannes

AU - Trittler, Rainer

AU - Kümmerer, Klaus

N1 - 2004 John Wiley & Sons, Ltd.

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Caspofungin (MK-0991; L-743,872) is the first representative of a new important class of antifungal agents, the glucan synthesis inhibitors. To the authors' best knowledge, to date only one high-performance liquid chromatography (HPLC) method has been published for the determination of caspofungin in serum. Severe difficulties with sorption were described. We developed a new method which addresses these difficulties using an advanced column-switching technique for fully automated analysis of caspofungin in serum without any pre-treatment. Extraction was performed automatically inline, using a diol column, followed by chromatography on a CN column. Detection was performed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) with isolation and fragmentation in the positive ion mode. Total analysis time was 30 min. Detection of caspofungin was achieved by retention time, isolation and fragmentation of the double positively charged caspofungin ion. This LC/MS assay was validated for between-run accuracy (max. 110%) and precision (max. CV 16.1%). The lower limit of quantification was 0.2 μg/mL. The analytical method with fully automated inline extraction of caspofungin described here removes the need for difficult and time-consuming sample pre-treatment. Sorption of caspofungin is not of importance. Additional advantages of the new method are that only a small quantity of serum (5 μL) is needed and that the method is very specific. Copyright © 2004 John Wiley & Sons, Ltd.

AB - Caspofungin (MK-0991; L-743,872) is the first representative of a new important class of antifungal agents, the glucan synthesis inhibitors. To the authors' best knowledge, to date only one high-performance liquid chromatography (HPLC) method has been published for the determination of caspofungin in serum. Severe difficulties with sorption were described. We developed a new method which addresses these difficulties using an advanced column-switching technique for fully automated analysis of caspofungin in serum without any pre-treatment. Extraction was performed automatically inline, using a diol column, followed by chromatography on a CN column. Detection was performed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) with isolation and fragmentation in the positive ion mode. Total analysis time was 30 min. Detection of caspofungin was achieved by retention time, isolation and fragmentation of the double positively charged caspofungin ion. This LC/MS assay was validated for between-run accuracy (max. 110%) and precision (max. CV 16.1%). The lower limit of quantification was 0.2 μg/mL. The analytical method with fully automated inline extraction of caspofungin described here removes the need for difficult and time-consuming sample pre-treatment. Sorption of caspofungin is not of importance. Additional advantages of the new method are that only a small quantity of serum (5 μL) is needed and that the method is very specific. Copyright © 2004 John Wiley & Sons, Ltd.

KW - accuracy

KW - AGENTS

KW - ANALYSIS

KW - antifungal

KW - ANTIFUNGAL AGENT

KW - ASSAY

KW - Caspofungin

KW - chromatography

KW - COLUMN

KW - column switching

KW - column-switching

KW - detection

KW - determination

KW - Electrospray

KW - EXTRACTION

KW - GERMANY

KW - HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

KW - HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

KW - HPLC

KW - human plasma

KW - INHIBITOR

KW - INHIBITORS

KW - Ionisation

KW - KNOWLEDGE

KW - LC

KW - MS

KW - liquid

KW - liquid chromatography

KW - LIQUID-CHROMATOGRAPHY

KW - mass spectrometry

KW - MASS-SPECTROMETRY

KW - Method

KW - MK-0991

KW - MODE

KW - pharmacokinetics

KW - PRETREATMENT

KW - QUANTIFICATION

KW - RABBITS

KW - retention

KW - Serum

KW - Sorption

KW - SPECTROMETRY

KW - tandem mass spectrometry

KW - URINE

KW - Chemistry

UR - http://www.scopus.com/inward/record.url?scp=9644266735&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/7166b00d-a772-3009-bb61-a1f761b5658b/

U2 - 10.1002/rcm.1691

DO - 10.1002/rcm.1691

M3 - Journal articles

C2 - 15517540

VL - 18

SP - 2871

EP - 2877

JO - Rapid Communications in Mass Spectrometry

JF - Rapid Communications in Mass Spectrometry

SN - 1097-0231

IS - 23

ER -