Determination of norgestimate and its metabolites in human serum using high-performance liquid chromatography with tandem mass spectrometric detection

Wong, Frankie A.; Edom, Richard W.; Duda, Michael P.; Tischio, John P.; Huang, Mike-Qingtao; Juzwin, Stephen J.; Tegegne, G.

doi:10.1016/s0378-4347(99)00353-9

Cited by 17 publications

(18 citation statements)

References 10 publications

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“…15 The assay procedure differed from that of the published method in that the chromatographic elution of extracted serum was accomplished via isocratic rather than gradient mode. The mobile phase consisted of water and acetonitrile (38:62, v/v) at a flow rate of 1.0 ml/min.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics of Norelgestromin and Ethinyl Estradiol Delivered by a Contraceptive Patch (Ortho Evra™/Evra™) under Conditions of Heat, Humidity, and Exercise

Abrams

Skee

Natarajan

et al. 2001

The Journal of Clinical Pharma

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The objectives of this randomized, open‐label, three‐period, incomplete block design study were to evaluate the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE) delivered by the contraceptive patch, Ortho EvraTM/EvraTM, and to evaluate patch adhesion under conditions of heat, humidity, and exercise. During each treatment period, 30 healthy women wore Ortho EvraTM on the abdomen for 7 days under one of six conditions (normal activity, sauna, whirlpool, treadmill, cool water immersion, ora combination of activities). Blood samples were collected before and several times to 240 hours after patch application. Mean serum concentrations of NGMN and EE generally remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, duringthe 7‐day wear period for all activities. Only 1 (1.1%) of 87 patches completely detached spontaneously. Peel force measurements were comparable for all activities. Ortho EvraTM was well tolerated. In conclusion, Ortho EvraTM delivers efficacious concentrations of NGMN and EE and maintains adhesive reliability through 7 days of wear even under conditions of heat, humidity, and exercise.

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Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics of Norelgestromin and Ethinyl Estradiol Delivered by a Contraceptive Patch (Ortho Evra™/Evra™) under Conditions of Heat, Humidity, and Exercise

Abrams

Skee

Natarajan

et al. 2001

The Journal of Clinical Pharma

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“…For phase I Studies 7 and 8, the primary objective was to evaluate the effect of lurasidone on other drugs (digoxin, a P-gp substrate, Study 7; midazolam, a CYP3A4 substrate, Study 8) by comparing the steady-state PK of the test drug administered alone or after steady-state dosing with lurasidone 120 mg/day. For Study 9, the primary objective was to evaluate the effect of lurasidone 40 mg on the PK of ethinyl estradiol and norelgestromin, the major active metabolite of norgestimate [7,8], after concomitant administration of a combination oral contraceptive product containing ethinyl estradiol 0.035 mg and norgestimate 0.180, 0.215, or 0.250 mg (Ortho TriCyclen ® ; Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ, USA) [9]. The secondary objective in all of the phase I studies was to evaluate the safety of concomitant administration of lurasidone and the interacting drugs.…”

Section: Introductionmentioning

confidence: 99%

Lurasidone drug-drug interaction studies: a comprehensive review

Chiu

Ereshefsky

Preskorn

et al. 2014

Drug Metabolism and Drug Interactions

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Background: To evaluate potential drug-drug interactions with the atypical antipsychotic lurasidone. Methods: Seven phase I studies were conducted to investigate the effects of repeated dosing of ketoconazole, diltiazem, rifampin, or lithium on the pharmacokinetics (PK) of single oral doses of lurasidone, or the effects of repeated dosing of lurasidone on the PK of digoxin, midazolam, or the oral contraceptive norgestimate/ethinyl estradiol. Two 6-week, phase III studies included evaluation of the potential for interaction between lurasidone and lithium or valproate. Maximum serum or plasma concentration (C max ) and area under the concentration-time curve (AUC) were calculated. Results: Concomitant ketoconazole administration resulted in a 6.8-fold increase in lurasidone C max and a 9.3-fold increase in lurasidone AUC; concomitant diltiazem administration resulted in 2.1-and 2.2-fold increases, respectively. Rifampin decreased lurasidone C max and AUC (one-seventh and onefifth of lurasidone alone, respectively). Steady-state dosing with lurasidone increased C max and AUC 0-24 (AUC from time 0 to 24 h postdose) of digoxin by 9% and 13%, respectively, and of midazolam by 21% and 44%, respectively. There were no significant interactions between lurasidone and lithium, valproate, ethinyl estradiol, or norelgestromin (the major active metabolite of norgestimate). Conclusions: Lurasidone PK is altered by strong cytochrome P450 (CYP) 3A4 inhibitors or inducers, and coadministration is contraindicated; whereas moderate CYP3A4 inhibitors have less effect, and lurasidone dosage restrictions are recommended. No dose adjustment

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“…Utilized technologies included UV spectrophotometry [11][12][13][14], voltammetry [15,16], liquid chromatography with UV detection [17][18][19][20][21], gas chromatography [22,23], radioimmunoassays (RIA) [24][25][26][27][28][29], and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [30][31][32][33][34][35][36][37][38][39][40][41][42][43]. For many years, RIA methods, often applied in pharmacokinetic studies, have been the most sensitive analytical procedures for the determination of synthetic progestins in biological samples.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies using LC-MS/MS technology were reported for the determination of synthetic progestins in human plasma or serum [30][31][32][33][34][35][36][37][38][39][40][41][42][43], other biological matrices [44][45][46], and aquatic environmental samples [23,[47][48][49]. For human specimen, only a few LC-MS/MS methods are designed for the multi-analyte quantification of progestins [33,39].…”

Section: Introductionmentioning

confidence: 99%

“…For human specimen, only a few LC-MS/MS methods are designed for the multi-analyte quantification of progestins [33,39]. Most assays are devoted to the quantification of a single progestin [30][31][32][33][34][35][36][37][41][42][43], with a majority measuring levonorgestrel [30][31][32][33][34][35][36]. An alternative analytical approach is the combined analysis of progestins and ethinylestradiol (EE) [38][39][40] as usually administered in OCs.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma

et al. 2011

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Co-administration of synthetic progestin containing hormonal contraceptives (HCs) and antiepileptic drugs (AEDs) is a common clinical situation which needs specific considerations due to drug interactions. Several studies have demonstrated that lamotrigine plasma levels are significantly decreased during co-medication with HCs, and that this interaction is associated with increased seizure frequency in most of the cases. Additionally, an increase in contraceptive failure and unintended pregnancy could be observed during co-medication. Hence, monitoring of progestin plasma levels in patients with AED co-medication is of interest. A rapid and reliable online solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (online SPE-LC-MS/MS) method using gradient elution in the LC domain was established and validated for the simultaneous quantitative determination of gestodene, dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in human plasma. The online SPE-LC-MS/MS method covered a quantification concentration range of 5-100 ng/ml for dienogest, 1-100 ng/ml for etonogestrel and 2-100 ng/ml for all other analytes. Stable isotope-labeled internal standards were used for analyte quantification based on selected reaction monitoring experiments. Inter- and intra-assay precision and accuracy were determined from quality control (QC) samples at the lower limits of quantification and at low, medium, and high concentration levels within the calibration range. Inter-assay reproducibility at the QC levels was better than 10% (relative standard deviation, RSD), accuracy at these levels ranged from -3.7% to 11.3%. Total extraction efficiency, tested at three concentrations, ranged from 92.5% to 106.4%. Matrix interferences were excluded by post-column infusion experiments. To prove the applicability of the assay in clinical cohorts, a sample set (n = 298) stemming from study patients under AED/oral HC co-medication was screened for progestin plasma levels. This method has to be considered a research-use-only assay and must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the IVD directive (98/79/EG) of the European Community.

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Determination of norgestimate and its metabolites in human serum using high-performance liquid chromatography with tandem mass spectrometric detection

Cited by 17 publications

References 10 publications

Pharmacokinetics of Norelgestromin and Ethinyl Estradiol Delivered by a Contraceptive Patch (Ortho Evra™/Evra™) under Conditions of Heat, Humidity, and Exercise

Pharmacokinetics of Norelgestromin and Ethinyl Estradiol Delivered by a Contraceptive Patch (Ortho Evra™/Evra™) under Conditions of Heat, Humidity, and Exercise

Lurasidone drug-drug interaction studies: a comprehensive review

Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma

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