Analysis of Nosiheptide in Food Animal Tissues via Its Unique Degradation Product by Liquid Chromatography–Tandem Mass Spectrometry after Alkaline Hydrolysis

Abstract

Very weak signals of fragment ions of nosiheptide could be observed using liquid chromatography−tandem mass spectrometry. The preparation of 4-hydroxymethyl-3-methyl-1H-indole-2-carboxylic acid (HMIA), a specific fragment of nosiheptide, by alkaline hydrolysis is described. HMIA showed a good mass spectrometric signal in negative electrospray ionization mode. In the new method, the nosiheptide residue in muscle tissue was hydrolyzed with sodium hydroxide aqueous solution; this was followed by cleanup using mixed mode cartridges. Identification and quantification of nosiheptide were carried out by analyzing HMIA in hydrolysate of muscles. Nosiheptide showed a good linear relationship (r > 0.996) in the calibration range of 2−500 μg/kg, and a low limit of quantification of 2 μg/kg was obtained in swine, chicken, and fish muscles. Recoveries of nosiheptide from spiked muscle samples were 85−108% with relative standard deviations less than 10%. The proposed method was successfully applied for the detection of the nosiheptide residue in medicated animal tissues samples.

Selective biosynthesis of a rhamnosyl nosiheptide by a novel bacterial rhamnosyltransferase

“…With a novel mode of action inhibiting protein biosynthesis (Harms et al., 2008 ), NOS demonstrates remarkable in vitro antibacterial activity against a range of drug‐resistant Gram‐positive pathogens including methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant Staphylococcus epidermidis (MRSE) and vancomycin‐resistant enterococci (VRE) (Bagley et al., 2015 ; Haste et al., 2012 ), even at concentrations in the ng/mL range. Accordingly, NOS was anticipated to serve as the latest last‐resort antibiotic for the clinical treatment of Gram‐positive bacterial infections; however, due to a lack of in vivo effects, NOS has typically been added to animal feed to prevent or alleviate intestinal bowel disease in livestock (Song et al., 2019 ; Xie et al., 2019 ).…”

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

“…Thiostrepton (Figure ) has potent anti-Gram-positive activity and is a component in veterinary topical ointment to treat interdigital cysts and infected anal glands of dogs and cats . A structurally similar thiopeptide, nosiheptide (Figure ), is highly active against several Gram-positive bacteria resistant to other antibiotics and is widely added into feed additives to promote growth and feed conversion in pigs and chickens . Besides, thiopeptide GE2270A (Figure ) displays potent activity against Gram-positives, including methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE), and group A streptococci .…”

“… 18 A structurally similar thiopeptide, nosiheptide ( Figure 2 ), is highly active against several Gram-positive bacteria resistant to other antibiotics and is widely added into feed additives to promote growth and feed conversion in pigs and chickens. 23 Besides, thiopeptide GE2270A ( Figure 2 ) displays potent activity against Gram-positives, including methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE), and group A streptococci. 24 Two semisynthetic analogues of GE2270A, i.e., LFF571 and CB-06-01 (now named NAI- Acne) have been completed Phase II clinical trials.…”