Quantitation of Insulin Analogue Glargine and Its Two Metabolites M1 and M2 on Triple Quad 6500 and Triple TOF 5600 LC-MS/MS Systems in a Dog Toxicokinetics Study

Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml

Insulin glargine is processed in vivo into soluble 21(A) -Gly-human insulin (M1), the principal moiety responsible for metabolic effects, and subsequently into M2. This sub-study compared metabolism and metabolite pharmacokinetic (PK) profiles of investigational new insulin glargine U300 (Gla-300) with insulin glargine 100 U/ml (Gla-100, Lantus®, Sanofi-Aventis Deutschland GmbH, Frankfurt am Ma...

Quantitation of Insulin Glargine and Major Metabolites in Human Plasma Using Hybrid LBA-LC/MS with Automated Magnetic Particle Processing

Pyrrolizidine Alkaloids: Characterization in Botanical and Dietary Supplements using Accurate-Mass Q-TOF LC/MS and All Ions MS/MS

Pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) have serious hepatotoxic effects in both humans and animals, necessitating a method capable of detecting, characterizing, and quantifying them using a robust assay. While triple quadrupole LC/MS systems are ideal for targeted detection, targeted analysis requires standards that are not always easily obtained. Only a fraction of known natu...

Metabolic effect and receptor signalling profile of a non-metabolisable insulin glargine analogue

CONTEXT Insulin glargine (GLA) is rapidly metabolized in vivo to metabolite M1, which has in vitro metabolic and mitogenic profiles comparable with human insulin (HI). OBJECTIVE To investigate the pharmacologic and signalling profiles of a non-metabolizable analogue (A21Gly,DiD-Arg) insulin (D-GLA). METHODS Rats were injected s.c. with 1, 12.5 or 200 U/kg of GLA or D-GLA; blood glucose and ...

Plasma Exposure to Insulin Glargine and Its Metabolites M1 and M2 After Subcutaneous Injection of Therapeutic and Supratherapeutic Doses of Glargine in Subjects With Type 1 Diabetes

OBJECTIVE In vivo, after subcutaneous injection, insulin glargine (21(A)-Gly-31(B)-Arg-32(B)-Arg-human insulin) is enzymatically processed into 21(A)-Gly-human insulin (metabolite 1 [M1]). 21(A)-Gly-des-30(B)-Thr-human insulin (metabolite 2 [M2]) is also found. In vitro, glargine exhibits slightly higher affinity, whereas M1 and M2 exhibit lower affinity for IGF-1 receptor, as well as mitogenic...