A modified LC-MS/MS method for the detection of whole blood tacrolimus and its clinical value in Chinese kidney transplant patients

Yu, Ke-Wei; Li, Bing-Ling; Yuan, Ying-Shi; Liao, Jia-Min; Li, Weikang; Dong, Heng; Ke, Peifeng; Jin, Xing; Chen, Lu; Zhao, Jingjing; Wang, Heng; Cao, Shunwang; Chen, Weiye; Huang, Xian-Zhang; Zhao, Beibei; Kang, Chun-Min

doi:10.1016/j.heliyon.2022.e10214

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…The separation of the two analytes was performed in 2.5 min with high accuracy and precision. The detection limit for both drugs was largely improved in this work as well (0.100-100 ng/ml for tacrolimus and 2.00-2,000 ng/ml for cyclosporine A) compared with the 0.3 ng/ml of tacrolimus reported by Yu et al (2022), Krnáč et al (2019) and Mei et al (2018), with which it was difficult to satisfy the TDM demand in clinical.…”

Section: Analytementioning

confidence: 75%

“…However, in their study, the samples were observed to be dirty and the internal normalized matrix effect factor of cyclosporine A was between 133.6 and 167.2%. Ke‐Wei Yu et al introduced an improved LC–MS/MS method for the detection of tacrolimus in whole blood and its clinical application in kidney transplant patients in China (Yu et al, 2022). The method was designed with two HPLC systems coupled with mass spectrometry to achieve the detection of two samples within 3.5 min.…”

Section: Resultsmentioning

confidence: 99%

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Improved LC–MS/MS method for the simultaneous quantification of tacrolimus and cyclosporine A in human blood and application to therapeutic drug monitoring

Chen,

Yang,

et al. 2023

Biomedical Chromatography

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In order to facilitate therapeutic drug monitoring of tacrolimus and cyclosporine A in clinical practice, a simple, rapid, robust, sensitive and specific LC–MS/MS assay was developed and validated for the simultaneous determination of tacrolimus and cyclosporine A in human whole blood. Erythrocytes were destroyed using internal standard solution with 10% (w/v) zinc sulfate in water. The analytes were extracted from 100 μl of whole blood by protein precipitation with acetonitrile. Chromatographic separation was conducted on a Kinetex PFP column (60°C) by a gradient elution with a flow rate of 0.450 ml/min in 2.5 min. Quantitative analysis was performed using electrospray ionization and multiple reaction monitoring in positive ionization mode. The method was fully validated as per current guidelines on bioanalytical methodologies of the US Food and Drug Administration and European Medicines Agency. The method developed was applied successfully in analyzing clinical samples from patients administered tacrolimus or cyclosporine A. The sample treatment procedure was rationalized and improved to fulfill the complete target extraction. The chromatography conditions were optimized to achieve rapid and accurate quantification of both analytes. This method may be beneficial as a constructive input for the therapeutic drug monitoring of tacrolimus and cyclosporine A in obtaining individualized therapy.

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Section: Analytementioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Improved LC–MS/MS method for the simultaneous quantification of tacrolimus and cyclosporine A in human blood and application to therapeutic drug monitoring

Chen,

Yang,

et al. 2023

Biomedical Chromatography

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“…Creatinine was measured using the Roche enzymatic assay, which has been reported to have an impression of 2.3%. 31 eGFR was calculated using both the modified Schwartz formula for patients younger than 18 years of age and the Cockroft-Gault formula for patients 18 years of age and older, 32,33 as well as the Pottel Full Age Spectrum for height formula for all ages. 34 Using the reference date of the LCPT prescription, eGFR values were calculated for converted patients nearest to time points of −6 months, 0 months, 6 months, and 12 months.…”

Section: Me Thodsmentioning

confidence: 99%

The use of once‐daily LCP‐Tacrolimus with adolescent and young adult solid organ transplant recipients

Householder,

Ramakrishnan,

Chen

et al. 2024

Pediatric Transplantation

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BackgroundAdolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once‐daily formulation of tacrolimus, LCP‐tacrolimus (LCPT), on medication adherence for AYA SOT patients.MethodsA retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single‐center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI).ResultsTwenty‐nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate‐acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost.ConclusionsLCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.

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“…However, there have been several reported cases of falsely elevated tacrolimus levels post-transplant, hypothesized to be due to circulating endogenous heterophile antibodies binding to the reagent, animal antibodies, used in the assay [6][7][8]. Liquid chromatography and tandem mass spectrometry (LC-MS) is considered the gold standard for monitoring tacrolimus levels due to its selectivity, sensitivity, and specificity [9][10][11]. However, LC-MS is not often used because it is time-intensive and more expensive.…”

Section: Introductionmentioning

confidence: 99%

Falsely Elevated Tacrolimus (FK506) Trough Levels in a Liver Transplant Recipient

Garg,

Mo,

Fitzmaurice

et al. 2024

Cureus

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Antibody-conjugated magnetic immunoassay (ACMIA) for tacrolimus (FK506) may detect falsely elevated tacrolimus trough levels, a commonly underreported event. We report a case of falsely elevated whole-blood tacrolimus levels in a patient post-orthotopic liver transplantation. A 71-year-old male patient underwent liver transplantation in 2012. Post-transplantation, the patient was immediately started on tacrolimus for maintenance immunosuppression. His most recent dose was 0.5 mg four times weekly. During monitoring, trough levels were at 25.9 ng/mL using ACMIA. After this result, a decision was made to hold tacrolimus. After holding tacrolimus for seven days, detected trough levels were still continually greater than 20 ng/mL. Upon suspicion of falsely elevated results, liquid chromatography with mass spectroscopy (LC-MS) was used to check tacrolimus trough levels. Results showed normal trough levels of 7.6 ng/mL. Because of its narrow therapeutic window, tacrolimus levels need to be carefully monitored throughout treatment. When high tacrolimus levels are detected using ACMIA without a correlating clinical scenario, trough levels should be re-confirmed using LC-MS to prevent clinical decisions from being made based on falsely elevated results.

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A modified LC-MS/MS method for the detection of whole blood tacrolimus and its clinical value in Chinese kidney transplant patients

Cited by 5 publications

References 30 publications

Improved LC–MS/MS method for the simultaneous quantification of tacrolimus and cyclosporine A in human blood and application to therapeutic drug monitoring

Improved LC–MS/MS method for the simultaneous quantification of tacrolimus and cyclosporine A in human blood and application to therapeutic drug monitoring

The use of once‐daily LCP‐Tacrolimus with adolescent and young adult solid organ transplant recipients

Falsely Elevated Tacrolimus (FK506) Trough Levels in a Liver Transplant Recipient

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