Preclinical pharmacokinetics of a promising antineoplastic prototype piperazine-containing compound (LQFM018) in rats by a new LC-MS/MS bioanalytical method

•High throughput and sensitive bioanalytical method for the LQFM018 quantification.•First and reliable determination of main pharmacokinetic LQFM018 parameters.•Primary kinetic understands of a new promising antineoplastic prototype.•Opening for further preclinical and clinical cancer research on LQ...

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Published in:	Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1223; p. 123710
Main Authors:	Rodrigues, Andryne R., Rodrigues, Caroline R., Gomes, Sandro A., Marques, Stefanne M., Naves, Lara M., Pedrino, Gustavo R., de Oliveira-Neto, Jerônimo R., de Carvalho, Flávio S., Cruz, Alessandro, Lião, Luciano M., Menegatti, Ricardo, Carlos da Cunha, Luiz
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-05-2023
Subjects:	Cancer research Drug development LC-MS/MS LQFM018 Preclinical pharmacokinetics LC-MS/MS Cancer research LQFM018 Drug development Preclinical pharmacokinetics
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Summary:	•High throughput and sensitive bioanalytical method for the LQFM018 quantification.•First and reliable determination of main pharmacokinetic LQFM018 parameters.•Primary kinetic understands of a new promising antineoplastic prototype.•Opening for further preclinical and clinical cancer research on LQFM018 activity. LQFM018 is a novel antineoplastic prototype, showing an expressive drug-triggered K562 leukemic cells death mechanism, through necroptotic signaling. Due to its promising effect, this study aimed to evaluate the pharmacokinetics of LQFM018 in rats, using a new validated bioanalytical LC-MS/MS-based method. Chromatographic column was an ACE® C18 (100 mm × 4.6 mm, 5 µm) eluted by a mobile phase composed of ammonium acetate 2 mM and formic acid 0.025%:methanol (50:50, v/v), under flow of 1.2 mL/min and injection volume of 3.0 µL. LQFM018 was extracted from rat plasma by a simple liquid–liquid method, using MTBE solvent. Rats were administered intraperitoneally at LQFM018 100 mg/kg dose and blood samples were collect at times of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 h. Bioanalytical-LC-MS/MS-based method was rapid, high throughput and sensitive with a good linearity ranging from 10 (LLOQ) to 15000 ng/mL, besides precise and accurate, ranging of 0.8–7.3% and 96.8–107.6%, respectively. The prototype LQFM018 was rapid and well absorbed, and highly distributed, apparently due to its high lipid solubility. These features are primordial for an anticancer agent in the treatment of deep tumors, such as bone marrow neoplasms, in which the drug might permeate easily tissue barriers. Also, LQFM018 has demonstrated a high clearance, according to a low t1/2in rats, indicating a relative fast elimination phase related to a possible intense hepatic biotransformation. These information support further studies to establish new understands on pharmacokinetics of promising antineoplastic prototype LQFM018 from preclinical and clinical evaluations.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1570-0232 1873-376X
DOI:	10.1016/j.jchromb.2023.123710