Evidence map›Paper›PMID 36557850›Full record

ArticleMolecules (Basel, Switzerland)2022

Determination of Leuprolide-Fatty Acid Conjugate in Rat Plasma Using LC-MS/MS and Its Pharmacokinetics after Subcutaneous Administration in Rats.

Gi-Sang Seong, Seong-Wook Seo, Ji Young Cho, Kye Wan Lee, Beom-Jin Lee, In-Soo Yoon, Hyo-Eon Jin

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Gi-Sang SeongCollege of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Seong-Wook SeoDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
Ji Young ChoCollege of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Kye Wan LeeDongkook Pharmaceutical Co., Ltd., Seoul 06072, Republic of Korea.
Beom-Jin LeeCollege of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.ORCID 0000-0003-0922-3289
In-Soo YoonDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.ORCID 0000-0002-0997-5723
Hyo-Eon JinCollege of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.ORCID 0000-0002-1292-5508
Ajou University · KRPusan National University · KRDongKook Pharmaceutical (South Korea) · KR

Funding

National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) 2022R1A2C1004714the Korea Evaluation Institute of Industrial Technology (KEIT) funded by the Ministry of Trade, Industry and Energy, Republic of Korea 20008840
6 · The paper itself

Abstract

Leuprolide is a synthetic nonapeptide drug (pyroGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt) that acts as a gonadotropin-releasing hormone agonist. The continuous administration of therapeutic doses of leuprolide inhibits gonadotropin secretion, which is used in androgen-deprivation therapy for the treatment of advanced prostate cancer, central precocious puberty, endometriosis, uterine fibroids, and other sex-hormone-related conditions. To improve the pharmacokinetic properties of peptide drugs, a fatty acid was conjugated with leuprolide for long-term action. In this study, we developed a simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of leuprolide and leuprolide-oleic acid conjugate (LOC) levels. The developed method was validated in terms of linearity, precision, accuracy, recovery, matrix effect, and stability according to the US Food and Drug Administration guidelines, and the parameters were within acceptable limits. Subsequently, the pharmacokinetics of leuprolide and LOCs were evaluated. In vivo rat subcutaneous studies revealed that conjugation with fatty acids significantly altered the pharmacokinetics of leuprolide. After the subcutaneous administration of fatty-acid-conjugated leuprolide, the mean absorption time and half-life were prolonged. To the best of our knowledge, this is the first study showing the effects of fatty acid conjugates on the pharmacokinetics of leuprolide using a newly developed UPLC-MS/MS method for the simultaneous quantification of leuprolide and LOCs.

Indexed as

LeuprolideProstatic NeoplasmsAndrogen AntagonistsAnimalsChromatography, High Pressure LiquidChromatography, LiquidFatty AcidsFemaleHumansMaleRatsTandem Mass SpectrometryAndrogen AntagonistsFatty AcidsLeuprolidecomparative pharmacokineticsfatty-acid-conjugated leuprolideleuprolidepeptideUPLC-MS/MS

Identifiers

PMID36557850
PMCPMC9786172
OpenAlexW4311959610

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.