Simultaneous determination of five novel luteinizing hormone-releasing hormone antagonists by LC–MS and pharmacokinetics in rats following cassette dosing

Yao, Jin-Feng; Zhou, Ning; Bai, Lu; Xu, Ping; Liu, Keliang; Xue, Ming

doi:10.1016/j.jchromb.2014.05.035

Cited by 4 publications

(1 citation statement)

References 31 publications

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“…7 Further, the microdialysis method avoids the issue of intermethodological variation when K p,uu values are obtained by extrapolation from various in vitro experimental methods. Although the skill-intensive and timeconsuming experimental procedures that are required by the use of brain microdialysis limit throughput in obtaining K p,uu values, recent progress in analytical procedures, such as highly sensitive liquid chromatographyemass spectrometry (LCeMS/MS), [8][9][10] has made it possible to overcome the through-put issue, at least in part, by means of the cocktail dosing approach. Thus, this approach offers the advantages of reducing the time required to develop CNS drugs and also reducing the number of animals used.…”

Section: Introductionmentioning

confidence: 99%

Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic–Cationic Drugs to the Brain

Kitamura

Okura

Higuchi

et al. 2016

Journal of Pharmaceutical Sciences

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Brain microdialysis is a powerful tool to estimate brain-to-plasma unbound concentration ratio at the steady state (Kp,uu) of compounds by direct measurement of the unbound concentration in brain interstitial fluid. Here, we evaluated a method to estimate Kp,uu values of multiple organic-cationic drugs simultaneously, by means of brain microdialysis combined with cocktail dosing. Five cationic drugs (diphenhydramine, memantine, oxycodone, pyrilamine, and tramadol), substrates of the proton-coupled organic cation antiport system, were selected as model drugs, and compared under single-dosing and cocktail-dosing conditions. We selected doses of the drugs at which no significant drug-drug interaction occurs at the proton-coupled organic cation antiport system in the blood-brain barrier (BBB). This was confirmed by uptake studies in hCMEC/D3 cells, an in vitro BBB model. The Kp,uu values after cocktail administration were in the range of 1.8-5.2, and were in good agreement with those after single administration. These results suggest that the microdialysis method with cocktail dosing is suitable to estimate Kp,uu values of several cationic drugs simultaneously, if there is no drug-drug interaction during BBB transport. The method could be useful for evaluating drug candidates with high Kp,uu values at an early stage in the development of central nervous system-acting drugs.

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Section: Introductionmentioning

confidence: 99%

Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic–Cationic Drugs to the Brain

Kitamura

Okura

Higuchi

et al. 2016

Journal of Pharmaceutical Sciences

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Quantitation of endogenous GnRH by validated nano-HPLC-HRMS method: a pilot study on ewe plasma

et al. 2022

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Gonadotropin-releasing hormone isoform I (GnRH), a neuro-deca-peptide, plays a fundamental role in development and maintenance of the reproductive system in vertebrates. The anomalous release of GnRH is observed in reproductive disorder such as hypogonadotropic hypogonadism, polycystic ovary syndrome (PCOS), or following prenatal exposure to elevated androgen levels. Quantitation of GnRH plasma levels could help to diagnose and better understand these pathologies. Here, a validated nano-high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) method to quantify GnRH in ewe plasma samples is presented. Protein precipitation and solid-phase extraction (SPE) pre-treatment steps were required to purify and enrich GnRH and internal standard (lamprey-luteinizing hormone-releasing hormone-III, l-LHRH-III). For the validation process, a surrogate matrix approach was chosen following the International Council for Harmonisation (ICH) and FDA guidelines. Before the validation study, the validation model using the surrogate matrix was compared with those using a real matrix such as human plasma. All the tested parameters were analogous confirming the use of the surrogate matrix as a standard calibration medium. From the validation study, limit of detection (LOD) and limit of quantitation (LOQ) values of 0.008 and 0.024 ng/mL were obtained, respectively. Selectivity, accuracy, precision, recovery, and matrix effect were assessed with quality control samples in human plasma and all values were acceptable. Sixteen samples belonging to healthy and prenatal androgen (PNA) exposed ewes were collected and analyzed, and the GnRH levels ranged between 0.05 and 3.26 ng/mL. The nano-HPLC-HRMS developed here was successful in measuring GnRH, representing therefore a suitable technique to quantify GnRH in ewe plasma and to detect it in other matrices and species. Graphical abstract

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Rapid screening of nine unradiolabeled candidate compounds as PET brain imaging agents using cassette-wave microdosing and LC-MS/MS

Sun

Xiao

Hong

et al. 2019

Journal of Chromatography B

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Simultaneous determination of five novel luteinizing hormone-releasing hormone antagonists by LC–MS and pharmacokinetics in rats following cassette dosing

Cited by 4 publications

References 31 publications

Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic–Cationic Drugs to the Brain

Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic–Cationic Drugs to the Brain

Quantitation of endogenous GnRH by validated nano-HPLC-HRMS method: a pilot study on ewe plasma

Rapid screening of nine unradiolabeled candidate compounds as PET brain imaging agents using cassette-wave microdosing and LC-MS/MS

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