Abstract
Lekethromycin, a new macrolide lactone, exhibits significant antibacterial activity. In this study, a reliable analytical ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UPLC-ESI-Orbitrap-MS) method was established and validated for the detection of lekethromycin in rat plasma. After a simple acetonitrile (ACN)-mediated plasma protein precipitation, chromatographic separation was performed on a Phenomenex Luna Omega PS C18 column (30 × 2.1 mm i.d. particle size = 3 μm) conducted in a gradient elution procedure using 0.5% formic acid (FA) in ACN and 0.5% FA in water as the mobile phase pumped at a flow rate of 0.3 mL/min. Detection was carried out under positive electrospray ionization (ESI+) conditions in parallel reaction monitoring (PRM) mode with observation of m/z 804.5580 > 577.4056 for lekethromycin and 777.5471 > 619.4522 for gamithromycin (internal standard, IS). The linear range was 5–1000 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter-day precision (expressed as relative standard deviation, RSD) values were ≤7.3% and ≤6.3%, respectively, and the accuracy was ≥90% ± 5.3%. The mean extraction recovery RSD valWeue was <5.1%. Matrix effects and dilution integrity RSD values were <5.6% and <3.2%, respectively. Lekethromycin was deemed stable under certain storage conditions. This fully validated method was effectively applied to study the pharmacokinetics of lekethromycin after a single intravenous administration of 5 mg/kg in rats. The main pharmacokinetic parameters were T1/2λz, CL_obs and VZ_obs were 32.33 ± 14.63 h, 0.58 ± 0.17 L/h/kg and 25.56 ± 7.93 L/kg, respectively.
Highlights
Macrolides are an important class of antibiotics widely prescribed for the treatment of human and veterinary infectious disease [1,2]
The majority of macrolide antibiotics are composed of a distinctive macrocyclic lactone ring to which one or more cladinose-neutral and desosamine-amino sugar residues are linked via glycosidic bonds [3,5]
This study established, for the first time, an ultra-performance-liquid chromatography system coupled to a Q-orbitrap mass spectrometry detector for the determination of lekethromycin in rat plasma
Summary
Macrolides are an important class of antibiotics widely prescribed for the treatment of human and veterinary infectious disease [1,2]. Of various Mycoplasmas, Rikettsia, Legionella pneumophila, Haemophilus influenzae and Chlamydia spp macrolide antibiotics have become an important alternative for patients allergic to penicillin [3,4]. It was reported that macrolides synthesis by reversible binding to the bacterial 50S ribosomal subunit [6,10,11,12,13,14,15] It was havethat good anti-inflammatory activity, resulting from activity, down-regulation thedown-regulation production and reported macrolides have good anti-inflammatory resulting of from secretion of proinflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-8.
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