Hong Kong Journal of Nephrology
Volume 7, Issue 2 , Pages 65-69, October 2005

Measurement of Whole Blood Tacrolimus Level by High Performance Liquid Chromatography Tandem Mass Spectrometry in Renal Transplant Recipients — A Single Center Perspective

  • Yiu-Han Chan

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • Corresponding Author InformationAddress correspondence and reprint requests to: Dr. Yiu-Han Chan, Department of Medicine, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR, China. Fax: (+852) 2384-4698
    • ,
  • Chung-Shun Ho

      Affiliations

    • Department of Chemical Pathology, Prince of Wales Hospital, Hong Kong SAR, China
    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Chi-Chung Shek

      Affiliations

    • Department of Pathology, Queen Elizabeth Hospital, Prince of Wales Hospital, Hong Kong SAR, China
    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Kim-Ming Wong

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Wai-Leung Chak

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Koon-Shing Choi

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Ka-Foon Chau

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China
    • ,
  • Chun-Sang Li

      Affiliations

    • Renal Unit, Department of Medicine, Prince of Wales Hospital, Hong Kong SAR, China

Article Outline

Background and Methods

Measurement of whole blood tacrolimus level by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was compared with that measured by microparticle enzyme immunoassay (MEIA) in 30 renal transplant recipients.

Results

Whole blood tacrolimus concentrations measured by HPLC-MS/MS were significantly lower than those measured by MEIA, with a median difference (interquartile range, IQR) of −0.40 μg/L (2.03 μg/L) (p < 0.0005). MEIA overestimated tacrolimus concentrations by a median (IQR) of 5.04% (19.5%). There was good correlation between the two methods (r = 0.94; p < 0.0005). The Passing-Bablok regression equation was: HPLC-MS/MS (μg/L) = 0.96 (95% confidence interval, CI, 0.91-1.00) × MEIA (μg/L) −0.02 (95% CI, −0.40-0.46). Bland-Altman analysis showed that the 95% limits of agreement were 2.98 to −4.10 μg/L. The 12-hour area under the concentration curve (AUC12) of tacrolimus derived using the two-point sampling equation with tacrolimus concentrations measured by HPLC-MS/MS was compared with that measured by MEIA. The AUC12 values calculated by the two methods were highly correlated (r = 0.90; p < 0.0005). The mean difference between the AUC12 values was 3.4 ± 11.6 hr.μg/L, and the mean percentage difference was 2.6 ± 11.4%, both of which were not statistically significant.

Conclusion

For tacrolimus concentrations within the recommended therapeutic range, the concentration measured by HPLC-MS/MS was statistically significantly lower than that measured by MEIA, but the difference was not clinically significant. Introduction of the more specific HPLC-MS/MS method does not require adjustment in the recommended tacrolimus trough concentration or the AUC12 level estimated by our abbreviated regression equation.

Key words:  drug concentration , HPLC-MS/MS , MEIA , kidney transplant , tacrolimus

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References 

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PII: S1561-5413(09)60216-7

doi:10.1016/S1561-5413(09)60216-7

Hong Kong Journal of Nephrology
Volume 7, Issue 2 , Pages 65-69, October 2005

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