Automated, fast and sensitive quantification of drugs in blood by liquid chromatography–mass spectrometry with on-line extraction: immunosuppressants

Christians, Uwe; Jacobsen, Wolfgang; Serkova, Natalie J.; Benet, Leslie Z.; Vidal, Christian; Sewing, K.‐Fr.; Manns, Michael P.; Kirchner, Gabriele I.

doi:10.1016/s0378-4347(00)00380-7

Cited by 167 publications

(128 citation statements)

References 39 publications

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“…For CsA measurement, a validated online extraction HPLC-tandem mass spectrometry assay was used. 37 See Supplemental Material for detailed methods.…”

Section: Measurement Of Adma and Intracellular Cyclosporine Levelsmentioning

confidence: 99%

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Renner¹,

Klawitter²,

Goldberg³

et al. 2013

Journal of the American Society of Nephrology

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Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.

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“…For CsA measurement, a validated online extraction HPLC-tandem mass spectrometry assay was used. 37 See Supplemental Material for detailed methods.…”

Section: Measurement Of Adma and Intracellular Cyclosporine Levelsmentioning

confidence: 99%

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Renner¹,

Klawitter²,

Goldberg³

et al. 2013

Journal of the American Society of Nephrology

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“…30 All tissues were weighed. Tissues were pulverized under liquid nitrogen, and 100 mg of the frozen tissue powder was measured into 1 mL of the 0.5 mol ⁄ L potassium phosphate buffer (pH 7.4) and homogenized.…”

Section: Ciclosporin Analysismentioning

confidence: 99%

The Effect of Ketoconazole on Whole Blood and Skin Ciclosporin Concentrations in Dogs

Gray¹,

Hillier²,

Cole³

et al. 2013

Advances in Veterinary Dermatology

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“…This procedure was much simpler than that used in previous studies. [9][10][11][12]16,17 and resulted in acceptable extraction recovery and precision for both cyclosporine and the IS.…”

Section: Sample Preparationmentioning

confidence: 99%

“…Many studies have been addressed specificity with regard to measurements of cyclosporine levels. [4][5][6][7][8] Recent studies have analyzed cyclosporine using HPLC-MS/ MS. [9][10][11][12] Also, some reports have been published on the simultaneous analysis of several immunosuppressant drugs (sirolimus, everolimus, and tacrolimus) [13][14][15][16][17] or the simultaneous analysis of cyclosporine metabolites. [18][19][20][21] These studies are time-consuming, and require many steps for sample preparation, including evaporation or reconstitution.…”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20][21] These studies are time-consuming, and require many steps for sample preparation, including evaporation or reconstitution. [9][10][11][12]16,17 UPLC-MS/MS has been used as an alternative to traditional HPLC, and has revolutionized the analysis of biological samples. UPLC provides increased resolution and sensitivity, reduced analysis time, and a lower cost per assay than HPLC.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Determination of Cyclosporine in Human Whole Blood by Ultra-Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry

et al. 2014

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Cyclosporine is an immunosuppressant drug used in organ transplants or for the treatment of autoimmune diseases. We developed and validated a simple, sensitive, and specific method using UPLC-MS/MS to determine cyclosporine levels in human whole blood. MS/MS detection was performed in the positive electrospray ionization mode with multiple reaction monitoring. Cyclosporine was extracted from whole-blood samples using ascomycin as an internal standard. The mass transitions m/z 1203.49 → 1185.53 and m/z 814.71 → 796.67 were used to assay the analyte and IS. This method was validated with respect to linearity, specificity, accuracy, precision, recovery, and stability. The method exhibited a linear response from 10 to 1000 ng mL -1 with correlation coefficient values >0.99. The precision and the accuracy values were within 15%, except at the lower limit of quatification (LLOQ). Cyclosporine was stable in whole blood with no evidence of degradation. This method was successfully applied to a pharmacokinetic study of cyclosporine in healthy volunteers following oral administration.Keywords Cyclosporine, UPLC-MS/MS, human whole blood

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Automated, fast and sensitive quantification of drugs in blood by liquid chromatography–mass spectrometry with on-line extraction: immunosuppressants

Cited by 167 publications

References 39 publications

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

The Effect of Ketoconazole on Whole Blood and Skin Ciclosporin Concentrations in Dogs

Quantitative Determination of Cyclosporine in Human Whole Blood by Ultra-Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry

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