Quantification of 6 Glucocorticoids in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Method Development, Validation, and Assessment of Matrix Effects

Sæves, Ingjerd; Vethe, Nils Tore; Bergan, Stein

doi:10.1097/ftd.0b013e3182241799

Cited by 10 publications

(5 citation statements)

References 18 publications

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“…Serum concentrations of etonogestrel were measured using a validated ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC/MS‐MS) method. The method was developed at the Department of Clinical Pharmacology, University Hospital of Linköping, from a method previously described by Seaves et al Detailed information on the method is found in Appendix S1.…”

Section: Methodsmentioning

confidence: 99%

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux‐en‐Y gastric bypass surgery: a pharmacokinetic study

Ginstman

Frisk

Carlsson

et al. 2018

BJOG

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Objective To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics. Design Single centre, open label, phase‐2 pharmacokinetic study. Setting University hospital of Linköping, Sweden. Population Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study. Methods Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry. Main outcome measures Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours). Results All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024). Conclusion To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously. Tweetable abstract The pharmacokinetics of oral desogestrel does not appear to change after gastric bypass surgery.

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Section: Methodsmentioning

confidence: 99%

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux‐en‐Y gastric bypass surgery: a pharmacokinetic study

Ginstman

Frisk

Carlsson

et al. 2018

BJOG

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“…We used a validated ultraperformance liquid chromatography/tandem mass spectrometry method (UPLC/MS-MS) to measure the serum concentrations of LNG. The method was developed at the Department of Clinical Pharmacology, University Hospital of Linköping, from a method previously described by Seaves et al [25]; this method was used in a previous study comparing desogestrel in women before and after RYGB [17]. The present study was performed in a very similar design, but no participants or result overlap between the studies.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls

et al. 2020

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Background Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives. Methods This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linköping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18–40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC 0–24h ) was the main outcome measure. Results There were no significant differences in the studied pharmacokinetic parameters, AUC 0–24h , total AUC, peak serum concentration ( C max ), time to peak serum concentrations ( T max ), apparent oral clearances of levonorgestrel (CL oral ), or terminal half-lives ( t ½) between the groups. Conclusion This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached. Clinical Trial Number EudraCT 2014–004677-17.

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“…In parallel experiments methylprednisolone (1000 μ g/L) was added or not to the combined treatment of tacrolimus and sirolimus for 24 hours at 37°C (5% CO 2 ). We used our previous investigation into the blood through concentrations of methylprednisolone after a bolus dose of 500 mg intravenously in liver transplant recipients, to select the dose to use in in vitro exposure [ 22 , 23 ]. We have also shown that 48 hours use of different doses of methylprednisolone to human islets in vitro reduced the viability and insulin secretion, without representing a durable detrimental effect [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human IsletsIn VitroCompared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

Kloster-Jensen

Sahraoui

Vethe

et al. 2016

Journal of Diabetes Research

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Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.

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Quantification of 6 Glucocorticoids in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Method Development, Validation, and Assessment of Matrix Effects

Abstract: A validated, sensitive, selective, and reproducible method for quantifying the concentrations of 6 glucocorticoids in human plasma by liquid chromatography tandem mass spectrometry is reported.

Cited by 10 publications

References 18 publications

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux‐en‐Y gastric bypass surgery: a pharmacokinetic study

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux‐en‐Y gastric bypass surgery: a pharmacokinetic study

Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls

Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human IsletsIn VitroCompared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

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