Quantification of unbound prednisolone, prednisone, cortisol and cortisone in human plasma by ultrafiltration and direct injection into liquid chromatrography tandem mass spectrometry

Ionita, Ileana A.; Akhlaghi, Fatemeh

doi:10.1258/acb.2010.010027

Cited by 15 publications

(4 citation statements)

References 28 publications

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“…In the salivary cortisol assay, the concentration of prednisolone had to exceed 125 nmol/L (45 g/L) before interference was observed at a level greater than the limit of quantitation of the assay and prednisone had to be present at a concentration greater than 31.3 nmol/L (11 g/L) to interfere in the salivary cortisone assay. The level of interference observed would not be clinically relevant, especially as these steroids would not be expected to reach concentrations in saliva which could give rise to significant interference [14]. Furthermore, it is also unlikely that patients being investigated for disorders of the HPA axis will be prescribed these steroids.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous analysis of cortisol and cortisone in saliva using XLC–MS/MS for fully automated online solid phase extraction

Jones

Owen

Adaway

et al. 2012

Journal of Chromatography B

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Section: Discussionmentioning

confidence: 99%

Simultaneous analysis of cortisol and cortisone in saliva using XLC–MS/MS for fully automated online solid phase extraction

Jones

Owen

Adaway

et al. 2012

Journal of Chromatography B

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“…Unbound glucocorticoids were measured using ultrafiltration of samples and online cleanup of the ultrafiltrate followed by LC-MS/MS analysis, as established in a method previously validated in our laboratory over a calibration range of 0.100 to 200 ng/mL for each analyte [16]. The method was slightly modified by performing the equilibration step of 300 μL plasma in open-top ultrafiltration devices for 4 h, at 37 °C, 10% CO 2 and 75% humidity, to insure that differences in pH due to multiple freeze-thaw cycles are corrected.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Total and Unbound Prednisone and Prednisolone in Stable Kidney Transplant Recipients With Diabetes Mellitus

Ionita

Ogasawara

Gohh

et al. 2014

Therapeutic Drug Monitoring

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Background and Objective The corticosteroid prednisone is an important component of post transplantation immunosuppressive therapy. Pharmacokinetic parameters of prednisone or its pharmacologically active metabolite, prednisolone, are not well characterized in transplant recipients. The objective of the present study was to compare the pharmacokinetics of total and unbound prednisone and prednisolone in diabetic and nondiabetic stable kidney transplant recipients and to evaluate the factors influencing plasma protein binding of prednisolone. Study Design Prednisone and prednisolone concentration-time profiles were obtained in 20 diabetic and 18 nondiabetic stable kidney transplant recipients receiving an oral dose of 5-10 mg prednisone per day. In addition to drug and metabolite exposures, factors influencing prednisolone protein binding were evaluated using a nonlinear mixed effects modeling approach. This model takes into account binding of prednisolone and cortisol to Corticosteroid Binding Globulin (CBG) in a saturable fashion and binding of prednisolone to albumin in a non-saturable fashion. Finally, we have investigated the influence of several covariates including diabetes, glucose concentration, hemoglobin A1c, creatinine clearance, body mass index, gender, age and time post transplantation on the affinity constant (K) between corticosteroids and their binding proteins. Results In diabetic patients, the values of dose-normalized area under the concentration-time curves were 27% and 23% higher for total and unbound prednisolone, respectively. Moreover, the ratio of total prednisolone to prednisone concentrations (active /inactive forms) was higher in diabetic subjects (P <0.001). Modeling protein binding results revealed that the affinity constant of CBG-prednisolone (KCBG,PL) was related to patient's gender and diabetes status. Conclusions Higher prednisolone exposure could potentially lead to the increased risk of corticosteroid related complications in diabetic kidney transplant recipients.

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“…Some very recent examples include the quantification of unbound prednisolone, prednisone, cortisol, and cortisone in human plasma by ultrafiltration–LC-MS [50] and the development of an ultrafiltration–LC-MS-based ligand-binding assay for Mycobacterium tuberculosis shikimate kinase [51], to be used for the development of antimicrobial agents. For screening of potential lead compounds in malaria drug discovery, work was performed for the drug targets Plasmodium falciparum thioredoxin and glutathione reductases [52].…”

Section: Affinity Selection—binding To Targets In Solutionmentioning

confidence: 99%

Recent developments in protein–ligand affinity mass spectrometry

Jonker¹,

Kool²,

Irth³

et al. 2010

Anal Bioanal Chem

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This review provides an overview of direct and indirect technologies to screen protein–ligand interactions with mass spectrometry. These technologies have as a key feature the selection or affinity purification of ligands in mixtures prior to detection. Specific fields of interest for these technologies are metabolic profiling of bioactive metabolites, natural extract screening, and the screening of libraries for bioactives, such as parallel synthesis libraries and small combichem libraries. The review addresses the principles of each of the methods discussed, with a focus on developments in recent years, and the applicability of the methods to lead generation and development in drug discovery.FigureSchematic view of the principle of filtration based 96-well affinity selection MS binding assays

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Quantification of unbound prednisolone, prednisone, cortisol and cortisone in human plasma by ultrafiltration and direct injection into liquid chromatrography tandem mass spectrometry

Cited by 15 publications

References 28 publications

Simultaneous analysis of cortisol and cortisone in saliva using XLC–MS/MS for fully automated online solid phase extraction

Simultaneous analysis of cortisol and cortisone in saliva using XLC–MS/MS for fully automated online solid phase extraction

Pharmacokinetics of Total and Unbound Prednisone and Prednisolone in Stable Kidney Transplant Recipients With Diabetes Mellitus

Recent developments in protein–ligand affinity mass spectrometry

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