Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Immunology‚ Endocrine and Metabolic Agents)

Ryuichi Morishita  
School of Medicine
Osaka University


Development of LC-MS/MS Quantification of the Novel Antimicrobial Peptide, SR-0379, and its Pharmacokinetics in Rats

Author(s): Hideki Tomioka, Hironori Nakagami, Tomokazu Sano, Kazuaki Takafuji, Seiji Takashima, Yasufumi Kaneda and Ryuichi Morishita

Affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development.


During the preclinical study of the original functional peptide, SR-0379, a sensitive liquid chromatographytandem mass spectrometry method was newly developed to study the pharmacokinetics of SR-0379 in rat plasma and subcutaneous tissue samples. Although SR-0379 was unstable in the rat plasma and subcutaneous tissue samples, pretreatment with EDTA and phosphoric acid (4 %) inhibited its degradation. The lower limits of quantification (LLOQ) for SR- 0379 were fully validated as 5 ng/ml in plasma and 5 ng/g in tissue with acceptable linearity, intra- and inter-assay precisions, and accuracy. Measurement of SR-0379 concentration in plasma after intravenous injection via LC-MS/MS yields plasma concentration-time curves (AUC0-∞) with areas of 667 ng•min/ml and an elimination half-life (t1/2) of 4.8 min. The concentration of SR-0379 in the subcutaneous tissue samples was 13.1 µg/g tissue at 30 minutes after a single dermal application (1 mg/ml, 50 µl) to a full-thickness excisional wound. Here, a highly sensitive and specific LC-MS/MS assay with a lower limit of quantification of 5 ng/ml was developed and validated to quantify SR-0379 in rat plasma. This method is useful for pharmacokinetic studies of the peptide drugs in rats.

Keywords: LC-MS/MS, pharmacokinetics, plasma, quantitation, subcutaneous tissue.

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Article Details

Page: [26 - 31]
Pages: 6
DOI: 10.2174/1871522213999131230123954