Skip to content
2000
Volume 21, Issue 17
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Dexamethasone (DEX), delivered through newly developed self-nanoemulsifying drug delivery systems, which is administered to rabbit eyes, has been presented. The instrumental parameters of the multiple LC-MS/MS methods in the literature are modified according to rabbit vitreous liquid and current laboratory conditions.

Methods

Quick optimization of the chromatographic and mass spectrometric parameters was done by inspecting the available literature for the analysis of DEX by LC-MS/MS from biological matrices. Chromatographic separation was achieved in the reverse mode using C18 (50x2.1 mm, 5 µm) as a stationary phase and acetonitrile and water with ammonium acetate as a mobile phase in gradient elution. Quantitation was done in multiple reaction monitoring (MRM) mode by following the transition of m/z 393 > m/z 373 in positive ion mode. The method was also validated in terms of selectivity, within-day accuracy and precision, linearity, and limit of detection (LOD). The extraction of DEX from rabbit vitreous liquid samples was carried out by protein precipitation using acetonitrile: water (70:30, v/v).

Results

DEX and beclomethasone (IS) were successfully separated and detected under optimized experimental settings. The method was selective for DEX and linear in the range of 0.5 and 250 ng/ml. The lower limit of quantification (LLOQ) was determined to be 0.238 ng/ml. The percent relative standard deviation (RSD) and recovery (%) of the low, medium, and high calibration levels were below 10% and within the range of 111%-114%, respectively. RSD (%) and recovery (%) of the LLOQ were below 17% and 82%, respectively. The validated method was successfully applied for the determination of pharmacokinetic properties of newly formulated dexamethasone self-nanoemulsifying drug delivery systems (DEXSNEDDS) used to administer DEX intravitreally to the rabbit.

Conclusion

LC-MS/MS conditions for the analysis of LC-MS/MS were determined by examining relevant literature for accomplishing simple and practical optimization of the experimental parameters, followed by method validation and analysis of rabbit vitreous liqiud. As conclusion, pharmacokinetic data of DEXSNEDDS has been obtained in the most accurate, sensitive, economical and rational way possible.

Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808291399240528095138
2024-06-05
2025-05-31
Loading full text...

Full text loading...

References

  1. KumarS. CookN. GumG. NaageshwaranV. NaageshwaranV. Characterization and validation of a chronic retinal neovascularization rabbit model by evaluating the efficacy of anti-angiogenic and anti-inflammatory drugs.Int. J. Ophthalmol.2022151152210.18240/ijo.2022.01.03 35047351
    [Google Scholar]
  2. PrajapatiB. PatelJ. Lipid-Based Drug Delivery Systems: Principles and Applications.New YorkJenny Stanford Publishing2023
    [Google Scholar]
  3. MohiteP. RajputT. PandhareR. SangaleA. SinghS. PrajapatiB.G. Nanoemulsion in management of colorectal cancer: Challenges and future prospects.Nanomanufacturing20233213916610.3390/nanomanufacturing3020010
    [Google Scholar]
  4. McClementsD.J. Nanoemulsions versus microemulsions: Terminology, differences, and similarities.Soft Matter2012861719172910.1039/C2SM06903B
    [Google Scholar]
  5. PrajapatiB.G. JivaniM. PaliwalH. Formulation and optimization of topical nanoemulsion based gel of mometasone furoate using 32 full factorial design.INDIAN DRUGS2021586192910.53879/id.58.06.12796
    [Google Scholar]
  6. SolansC. IzquierdoP. NollaJ. AzemarN. Garcia-CelmaM.J. Nano-emulsions.Curr. Opin. Colloid Interface Sci.2005103-410211010.1016/j.cocis.2005.06.004
    [Google Scholar]
  7. Chang-LinJ.E. AttarM. AcheampongA.A. RobinsonM.R. WhitcupS.M. KuppermannB.D. WeltyD. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant.Invest. Ophthalmol. Vis. Sci.2011521808610.1167/iovs.10‑5285 20702826
    [Google Scholar]
  8. EarlaR. BodduS.H.S. CholkarK. HariharanS. JwalaJ. MitraA.K. Development and validation of a fast and sensitive bioanalytical method for the quantitative determination of glucocorticoids—Quantitative measurement of dexamethasone in rabbit ocular matrices by liquid chromatography tandem mass spectrometry.J. Pharm. Biomed. Anal.201052452553310.1016/j.jpba.2010.01.015 20172680
    [Google Scholar]
  9. FerreiraM.S. MarquezC.R. dos SantosD.A. GabbaiJ.J. MarthoA.C. Yamanouchi BrandãoA.H. BarellaK.A. RiccioM.F. NoboliA.C. JúniorP.S. Validation of direct method to quantify dexamethasone in human aqueous humor by LC–MS/MS.Bioanalysis201810171361137010.4155/bio‑2018‑0079 30182725
    [Google Scholar]
  10. HuangZ. YangW. ZongY. QiuS. ChenX. SunX. ZhouY. XieZ. GaoQ. A study of the dexamethasone sodium phosphate release properties from a periocular capsular drug delivery system.Drug Deliv.201623383984710.3109/10717544.2014.919543 24865291
    [Google Scholar]
  11. ShenJ. DurairajC. LinT. LiuY. BurkeJ. ShenJ. Ocular pharmacokinetics of intravitreally administered brimonidine and dexamethasone in animal models with and without blood–retinal barrier breakdown.Invest. Ophthalmol. Vis. Sci.2014552105610.1167/iovs.13‑13650
    [Google Scholar]
  12. SamtaniM.N. JuskoW.J. Quantification of dexamethasone and corticosterone in rat biofluids and fetal tissue using highly sensitive analytical methods: Assay validation and application to a pharmacokinetic study.Biomed. Chromatogr.200828827828810.1002/bmc 17385808
    [Google Scholar]
  13. ChenY.L. JiangX. WengN. A liquid chromatographic-tandem mass spectrometric method for the quantitative analysis of dexamethasone in human plasma.J. Liq. Chromatogr. Relat. Technol.20022591317133410.1081/JLC‑120004749
    [Google Scholar]
  14. GongW. LiuS. XuP. FanM. XueM. Simultaneous quantification of diazepam and dexamethasone in plasma by high-performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic comparison between normoxic and hypoxic rats.Molecules20152046901691210.3390/molecules20046901 25913929
    [Google Scholar]
  15. YuanY. ZhouX. LiJ. YeS. JiX. LiL. ZhouT. LuW. Development and validation of a highly sensitive LC‐MS/MS method for the determination of dexamethasone in nude mice plasma and its application to a pharmacokinetic study.Biomed. Chromatogr.201529457858310.1002/bmc.3316 25165023
    [Google Scholar]
  16. CeccatoF. ArtusiC. BarbotM. LizzulL. PinelliS. CostantiniG. NieroS. AntonelliG. PlebaniM. ScaroniC. Dexamethasone measurement during low-dose suppression test for suspected hypercortisolism: Threshold development with and validation.J. Endocrinol. Invest.20204381105111310.1007/s40618‑020‑01197‑6 32060745
    [Google Scholar]
  17. ShuC. ZengT. GaoS. XiaT. HuangL. ZhangF. ChenW. LC–MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.2016102811111910.1016/j.jchromb.2016.06.009 27336703
    [Google Scholar]
  18. TaylorR.L. GrebeS.K. SinghR.J. Quantitative, highly sensitive liquid chromatography-tandem mass spectrometry method for detection of synthetic corticosteroids.Clin. Chem.200450122345235210.1373/clinchem.2004.033605 15486026
    [Google Scholar]
  19. DamonteG. SalisA. RossiL. MagnaniM. BenattiU. High throughput HPLC-ESI-MS method for the quantitation of dexamethasone in blood plasma.J. Pharm. Biomed. Anal.200743137638010.1016/j.jpba.2006.06.042 16887316
    [Google Scholar]
  20. DjedovicN.K. RainbowS.J. Detection of synthetic glucocorticoids by liquid chromatography-tandem mass spectrometry in patients being investigated for Cushing’s syndrome.Ann. Clin. Biochem.201148654254910.1258/acb.2011.010250 21846739
    [Google Scholar]
  21. YangY. LiH. GaoK. LiuM. SunY. YanT. FawcettJ.P. CuiY. GuJ. Simultaneous quantitation of dexamethasone palmitate and dexamethasone in human plasma by liquid chromatography/tandem mass spectrometry.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.20088621-211912410.1016/j.jchromb.2007.11.033 18164670
    [Google Scholar]
  22. ChenD. TaoY. LiuZ. LiuZ. WangY. HuangL. YuanZ. Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of glucocorticoid residues in edible tissues of swine, cattle, sheep, and chicken.Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess.201027101363137110.1080/19440049.2010.492530 20658401
    [Google Scholar]
  23. del AmoE.M. UrttiA. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.Exp. Eye Res.201513711112410.1016/j.exer.2015.05.003 25975234
    [Google Scholar]
  24. KomesliY. Burak OzkayaA. Ugur ErgurB. KirilmazL. KarasuluE. Design and development of a self-microemulsifying drug delivery system of olmesartan medoxomil for enhanced bioavailability.Drug Dev. Ind. Pharm.20194581292130510.1080/03639045.2019.1607868 30986085
    [Google Scholar]
  25. Üstündağ-OkurN. GökçeE.H. BozbıyıkD.İ. EğrilmezS. ÖzerÖ. ErtanG. Preparation and in vitro–in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis.Eur. J. Pharm. Sci.20146320421510.1016/j.ejps.2014.07.013 25111119
    [Google Scholar]
  26. KnychH.K. WeinerD. ArthurR.M. BadenR. McKemieD.S. KassP.H. Serum concentrations, pharmacokinetic/pharmacodynamic modeling, and effects of dexamethasone on inflammatory mediators following intravenous and oral administration to exercised horses.Drug Test. Anal.20201281087110110.1002/dta.2862 32436346
    [Google Scholar]
  27. Van Den HauweO. DumoulinF. AntignacJ.P. BoucheM.P. ElliottC. Van PeteghemC. Liquid chromatographic-mass spectrometric analysis of 11 glucocorticoid residues and an optimization of enzymatic hydrolysis conditions in bovine liver.Analytica Chimica. Acta20024731-2127134
    [Google Scholar]
  28. Van den HauweO. SchneiderM. SahinA. Van PeteghemC.H. NaegeliH. Immunochemical screening and liquid chromatographic-tandem mass spectrometric confirmation of drug residues in edible tissues of calves injected with a therapeutic dose of the synthetic glucocorticoids dexamethasone and flumethasone.J. Agric. Food Chem.200351132633010.1021/jf020533m 12502428
    [Google Scholar]
  29. WatteynA. WynsH. PlessersE. RussoE. De BaereS. De BackerP. CroubelsS. Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in broiler chickens.Vet. J.2013195221622010.1016/j.tvjl.2012.06.026 22835862
    [Google Scholar]
  30. KomesliY. YildirimY. KarasuluE. Visualisation of real-time oral biodistribution of fluorescent labeled self-microemulsifying drug delivery system of olmesartan medoxomil using optical imaging method.Drug Metab. Pharmacokinet.20213610036510.1016/j.dmpk.2020.10.004
    [Google Scholar]
/content/journals/lddd/10.2174/0115701808291399240528095138
Loading
/content/journals/lddd/10.2174/0115701808291399240528095138
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keyword(s): dexamethasone; DEXSNEDDS; LC-MS/MS; nanoemulsions; pharmacokinetics; rabbit vitreous liquid
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test