Simultaneous determination of glimepiride and its metabolites in human plasma by liquid chromatography coupled to a tandem mass spectrometry

Noh, Kyeumhan; Kim, Eun Young; Jeong, Tae-Cheon; Na, MinKyun; Baek, Moon‐Chang; Liu, Kwang-Hyeon; Park, Pil-Hoon; Shin, Beom Soo; Kang, Wonku

doi:10.1007/s12272-011-1210-0

Cited by 8 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[12] Subsequently, several research groups developed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative determination of glimepiride in human plasma. [13,14] Recently, the effect of SUs on biochemical changes in patients with T2DM was investigated through the metabolomic approach. [15] However, the effects of glimepiride on endogenous metabolomic alterations in healthy subjects remain poorly understood.…”

Section: Transl Clin Pharmacolmentioning

confidence: 99%

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

Young

Gwon

Kim

et al. 2017

Transl Clin Pharmacol

View full text Add to dashboard Cite

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre-and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

show abstract

Section: Transl Clin Pharmacolmentioning

confidence: 99%

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

Young

Gwon

Kim

et al. 2017

Transl Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…Glimepiride, a third‐generation sulfonylurea hypoglycemic agent, has been used for the treatment of type 2 noninsulin‐dependent diabetes mellitus 16,17 . The glimepiride metabolite appears to be formed by CYP2C9 in liver microsomes 18 . Although the efficacy of ginsenoside Rg3 and glimepiride in T2DM was confirmed by these studies, the mechanism of the effect of drug–drug interaction between ginsenoside Rg3 and glimepiride on cytochrome P450 enzymes is still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry

Yang

et al. 2021

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Rationale Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes. Methods An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra‐performance liquid chromatography coupled with quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap MS). Results The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1–M5) of glimepiride were found, and they were named 3N‐hydroxyglimepiride, hydroxyglimepiride, 1,2‐epoxy ether‐3‐hydroxyglimepiride, 1N‐hydroxyglimepiride and 1N,2C,S,O,O‐epoxy ether‐3‐hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2. Conclusions An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.

show abstract

“…Sitagliptin, one of the major DPP4 inhibitors, is eliminated primarily by renal excretion and only 16% of dose excreted as metabolites [5]. On the other hand, glimepiride, a second-generation sulfonylurea, is converted into M1 by CYP2C9 and carboxyl derivatives M2 by cytosolic enzymes [6]. Although several studies have demonstrated the safety of DPP4 inhibitors, studies directly comparing the effects and safety of SU upward titration treatment and combination treatment with low-dose SU and DPP4 inhibitors in Japanese diabetes patients have not been performed.…”

Section: Introductionmentioning

confidence: 99%

Effects of Sitagliptin on Pancreatic Beta-Cells in Type 2 Diabetes With Sulfonylurea Treatment: A Prospective Randomized Study

Sato

Takei

Hiramatsu³

et al. 2019

J Clin Med Res

View full text Add to dashboard Cite

BackgroundThis prospective randomized, multicenter, open-label, comparative study was performed to analyze the effects of sitagliptin on glycemic control and maintenance of beta-cell function in patients with poorly controlled type 2 diabetes treated with low-dose glimepiride.MethodsForty-one patients with type 2 diabetes mellitus treated with low-dose glimepiride (≤ 2 mg/day) were prospectively enrolled in this study (age: 20 - 75 years; hemoglobin A1c (HbA1c): 7.4- 9.4%). The patients were randomized into two groups: the glimepiride (G) group, in which glimepiride dose was increased gradually to 6 mg/day, and the sitagliptin (S) group, in which sitagliptin was added at a dose of 50 mg/day.ResultsHbA1c level was significantly decreased after 24 weeks, but not 12 weeks, in the G group, while a significant decrease was seen after 12 weeks in the S group. Although there were no significant differences in HbA1c level at 24 weeks between the two groups (P = 0.057). The overall trend of changes in HbA1c level suggested that the glucose-lowering effects were superior in the S group. Furthermore, a significant change in fasting glucose was seen in the S group, but not in the G group. Glycemic control target was achieved in 36.7% and 16.7% patients in the S group and the G group, respectively. The proinsulin/insulin (P/I) ratio was significantly increased in the G group, whereas it tended to decrease in the S group. After 24 weeks of treatment, no significant difference was observed in the P/I ratio between the two groups, whereas a significant difference was noted in the ΔP/I (amount of change). Albuminuria tended to increase in the G group compared with the S group.ConclusionThe results of the present study suggested that sitagliptin effectively lowered hyperglycemia and that it may have a protective effect on pancreatic beta-cells when combined with a low dose of glimepiride. Therefore, sitagliptin may represent a useful combination therapy with low-dose sulfonylurea, not only for achieving glycemic control but also for protection of pancreatic beta-cells.

show abstract

Simultaneous determination of glimepiride and its metabolites in human plasma by liquid chromatography coupled to a tandem mass spectrometry

Cited by 8 publications

References 11 publications

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry

Effects of Sitagliptin on Pancreatic Beta-Cells in Type 2 Diabetes With Sulfonylurea Treatment: A Prospective Randomized Study

Contact Info

Product

Resources

About