High-performance liquid chromatographic determination of cyclosporin A in human plasma and urine

Niederberger, Werner; Schaub, Peter; Beveridge, T.

doi:10.1016/s0378-4347(00)81500-5

Cited by 71 publications

(10 citation statements)

References 3 publications

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“…The results show that it is possible to analyze these closely structural related peptides directly in biological matrices such as CSF, indicating the large selectivity of this rapid multidimensional system. The CLOQ of the enkephalins in this system is 2.5 mg/mL, which is comparable to the CLOQ in the earlier presented SEC-LC system [25] and sufficient for the analysis of exogenous peptides used as drugs [30][31][32]. Both CLOQ values cannot be increased by increasing the injection volume higher than 10 mL.…”

Section: Conclusion and Future Perspectivessupporting

confidence: 54%

On‐line coupling of size exclusion and capillary zone electrophoresis via a reversed‐phase C18 trapping column for the analysis of structurally related enkephalins in cerebrospinal fluid

et al. 2003

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On-line coupled analytical techniques can be advantageous in the assay of smaller peptides in complex biological matrices such as plasma, cerebrospinal fluid (CSF) and tissues. The present study shows the feasibility of a recently developed system, consisting of a size-exclusion chromatographic (SEC) separation followed by a trapping procedure on an RP18 microcolumn with subsequent elution of the trapped fraction and separation by capillary zone electrophoresis (CZE) for the quantification of structural-related peptides in biological matrices, as demonstrated for a number of enkephalins in CSF. After SEC separation of the enkephalins from large proteins present in CSF a heart-cut of 200 nuL, containing the enkephalin peak, is taken, concentrated on the RP18 microcolumn and, after elution of the enkephalins with 80% acetonitrile, a fraction of the eluate is electrokinetically injected into the CZE system, where stacking and separation is achieved. The degradation of the peptides, caused by endogenous peptidases in the matrix, is sufficiently inhibited with imipramine HCl. The assay has a satisfactory linearity and intraday (9.70-16.3%) precision considering the complexity of this multidimensional separation system. The sensitivity of the method, with a concentration limit of quantification of 2.5 nug/mL, is comparable with other CZE assays for peptides and sufficient for the quantification of peptide drugs in biological matrices.

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Section: Conclusion and Future Perspectivessupporting

confidence: 54%

On‐line coupling of size exclusion and capillary zone electrophoresis via a reversed‐phase C18 trapping column for the analysis of structurally related enkephalins in cerebrospinal fluid

et al. 2003

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“…HPLC is specific for unchanged CyA (60). The unchanged CyA exhibits a high immunosuppressive potency, whereas the metabolites of CyA possess no or only questionable immunosuppressive activity (61-63).…”

Section: Resultsmentioning

confidence: 99%

Impaired liver function in stable renal allograft recipients

et al. 1989

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Hepatic failure as a cause of death is increased in stable renal allograft recipients when compared with patients on dialysis. In order to assess the magnitude and the natural history of the hepatic functional derangement, the kinetics of xenobiotics which are metabolized by cytosolic (galactose) or microsomal (prednisolone, cyclosporine A) enzymes were determined in 28 consecutive stable kidney transplant patients 1 month and 1 year after transplantation. Renal transplant patients had a decreased mean (+/- S.D.) galactose elimination capacity at 1 month (6.26 +/- 0.94 mg per min x kg) and at 1 year (5.93 +/- 0.96 mg per min x kg), when compared with a different group of 28 healthy control subjects (7.52 +/- 0.78 mg per min x kg, p less than 0.001) and a decreased total body clearance of prednisolone at 1 month (2.13 +/- 0.34 ml per min x kg vs. 2.71 +/- 0.43 ml per min x kg in controls, p less than 0.001), which further decreased over the following year to 1.76 +/- 0.32 ml per min x kg (p less than 0.001). The clearance of cyclosporine A declined significantly during the first year of successful transplantation (5.9 +/- 2.1 ml per min x kg vs. 4.9 +/- 1.2 ml per min x kg, p less than 0.05). In conclusion, a substantial proportion of stable renal transplant recipients have decreased cytosolic and microsomal liver functions despite the absence of clinical and laboratory evidence of significant liver disease.

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“…48 Cyclosporin and the internal standard, cyclosporin D (CyD), were extracted from plasma or whole blood with diethyl ether and then separated by chromatography on a reversed phase CI8 column at 75°C. The mobile phase was a gradient of an increasing proportion of acetonitrile in methanol and ultraviolet (UV) absorption detection was used.…”

Section: High-performance Liquid Chromatographymentioning

confidence: 99%

Methodological and Clinical Aspects of Cyclosporin Monitoring: Report of the Association of Clinical Biochemists Task Force

Holt¹,

Johnston

et al. 1994

Ann Clin Biochem

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Additional key phrases: immunosuppressant drugs; analytical methods; transplantationDuring the last decade a growing number of centres have become involved in the measurement of the immunosuppressive agent cyclosporin, When the UK Cyclosporin Quality Assessment Scheme (UKCQAS) was started by two of us (DH and AI) in 1984 there were 14 participants in the UK; now there are over 50. The increasing number of indications for which cyclosporin can be prescribed, together with the proliferation of centres capable of performing organ transplantation, suggests that an even larger number of laboratories are likely to offer this assay as a service in the future. The purpose of this review is to summarize current information relating to cyclosporin monitoring and to give some indication of the clinical problems surrounding the use of the results. It has been written against the background of three consensus documents, based on input from laboratory scientists and clinicians, all of which have arrived at similar concluslons.l ? Since these consensus reports were written there have been some changes with regard to the immunoassays available for cyclosporin measurement and there have been a number of reports documenting the performance of the newest assays.The present authors have all been involved in the measurement of cyclosporin in a variety of clinical settings and intend that this review should allow laboratory workers and clinicians to make an informed choice when deciding which method to use for the measurement of cyclosporin. To this end we have drawn upon recent literature, Correspondence: Dr D W Holt. 420 our own experience in this field, data from the UKCQAS, and we have surveyed current practices in UK laboratories performing the measurement.We have chosen to concentrate on three main areas. First, the pharmacology of the drug, since this is essential to an appreciation of the methodological problems associated with cyclosporin measurement. Secondly, we have produced a detailed review of analytical methods and their relative performance. Thirdly, we present a summary of the clinical factors which influence the interpretation of the results in the diverse clinical settings in which cyclosporin is used, to provide those who are producing the cyclosporin results with some insight into the problems faced by those who have to use the data. CYCLOSPORINSince the cyclic peptide cyclosporin (cyclosporin A, ciclosporin, cyclosporine, Sandimmun@) began to be included in immunosuppressive protocols, it has had a profound effect on clinical transplantation world-wide, not only in terms of improved organ and patient survival but also in improving more positive public attitudes towards transplantation. One major disappointment which emerged with the clinical use of cyclosporin was that therapeutic doses in man caused a number of adverse side-effects, in contrast to many of the animal species studied. These sideeffects included renal and hepatic dysfunction, hypertension, neurotoxicity, lymphoma, abnormal glucose homeostasis, hyp...

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High-performance liquid chromatographic determination of cyclosporin A in human plasma and urine

Cited by 71 publications

References 3 publications

On‐line coupling of size exclusion and capillary zone electrophoresis via a reversed‐phase C18 trapping column for the analysis of structurally related enkephalins in cerebrospinal fluid

On‐line coupling of size exclusion and capillary zone electrophoresis via a reversed‐phase C18 trapping column for the analysis of structurally related enkephalins in cerebrospinal fluid

Impaired liver function in stable renal allograft recipients

Methodological and Clinical Aspects of Cyclosporin Monitoring: Report of the Association of Clinical Biochemists Task Force

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