Liquid chromatography-tandem mass spectrometry for the monitoring of theophylline concentration in serum and its application to external quality assessment

doi:10.3969/j.issn.1673-8640.2014.11.016

Abstract

Abstract:

Objective　To perform the methodology evaluation of a liquid chromatography-tandem mass spectrometry（LC-MS/MS） for the determination of theophylline in serum， and to investigate the application significance in the therapeutic drug monitoring（TDM） for theophylline. Methods　After being added with radionuclide theophylline-D6 as internal standard， serum samples were treated with protein precipitation and determined by LC-MS/MS. A reverse phase chromatographic separation was performed on Capcell C18 MG Ⅲ analytical column（100 mm×2.0 mm， 5 μm） by using 0.1% formic acid in acetonitrile and 0.1% formic acid in water [20∶80（v/v）] as mobile phase. The flow rate was 0.3 mL/min. Theophylline and internal standard were monitored by a positive electrospray ion-tandem mass spectrometry system. The proficiency performance of LC-MS/MS was tested by participation to external quality assessment of theophylline TDM for the National Center for Clinical Laboratory. Results　The linear range of LC-MS/MS for the determination of theophylline was 1-50 μg/mL. The accuracy was 94.14%-104.00% with within-run and between-run precisions of 2.26%-6.65% and 4.70%-6.84%. The run time was 3.5 min per sample. Stabilities were good under 3 cycles of frozen-thaw for 3 times from -30 ℃ to room temperature， room temperature for 24 h， autosampler for 24 h and -30℃ for 28 d. The external quality assessment proficiency test showed the bias of 2.75%， regression slope of 1.04 and correlation coefficient（r²） of 0.983. Conclusions　The radionuclide internal standard-dilution LC-MS/MS is simple， rapid， specific and sensitive for the determination of serum theophylline. It is comparable with the external quality assessment proficiency test for consecutive 6 years， and it is suitable for theophylline TDM in clinical practice.

Key words: Theophylline, Liquid chromatography-tandem mass spectrometry, Therapeutic drug monitoring, External quality assessment

CLC Number:

R974

SUN Xuying, ZHANG Meiwei, LI Shuijun. Liquid chromatography-tandem mass spectrometry for the monitoring of theophylline concentration in serum and its application to external quality assessment[J]. , 2014, 29(11): 1144-1150.

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