毛细管GC法测定格列齐特片和格列齐特片（Ⅱ）的含量

目的建立毛细管GC法测定格列齐特片和格列齐特片（Ⅱ）的含量。方法以正十四烷为内标,采用DB-624毛细管柱,FID检测器,甲醇为溶剂。结果格列齐特在0.15～1.5mg/ml浓度范围内线性关系良好,线性方程R=1.251c-0.024,r=0.9995（n=6）。平均回收率为99.49%和99.61%,RSD为0.65%和0.52%。结论本法可用于测定格列齐特片和格列齐特片（Ⅱ）的含量,方法灵敏、简便、准确。     

A Supercritical Fluid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Quantification of Metformin and Gliclazide in Human Plasma

Present study reports the development and validation of a simultaneous estimation of metformin and gliclazide in human plasma using supercritical fluid chromatography followed by tandem mass spectrometry. Acetonitrile:water (80:20) mixture was used as a mobile phase along with liquid CO₂ in supercritical fluid chromatography and phenformin as an internal standard. The modified plasma samples were analyzed by electro-spray ionization method in selective reaction monitoring mode in tandem mass spectrometry. Supercritical fluid chromatographic separation was performed using nucleosil C₁₈ containing column as a stationary phase. The separated products were identified by characteristic peaks and specific fragments peaks in tandem mass spectrometry as m/z 130 to 86 for metformin, m/z 324 to 110 for gliclazide and m/z 206 to 105 for phenformin. The present method was found linear in the concentration ranges of 6.0-3550 ng/ml and 7.5-7500 ng/ml for metformin and gliclazide, respectively. Pharmacokinetic study was performed after an oral administration of dispersible tablets containing 500 mg of metformin and 80 mg of gliclazide using same techniques.     

Comparison of ultraviolet detection,evaporative light scattering detection and charged aerosol detection methods for liquid-chromatographic determination of anti-diabetic drugs

Recently, charged aerosol detection (CAD), a new kind of universal detection method, has been widely employed in the HPLC system. In the present study, four kinds of anti-diabetic drug standards, glipizide, gliclazide, glibenclamide and glimepiride were determined by ultraviolet (UV) detection, evaporative light scattering detection (ELSD) and the aforementioned CAD. The results were compared with reference to linearity, accuracy, precision and limit of detection (LOD). All of the experiments were performed on a reverse phase column with water and acetonitrile as the mobile phase. Separations were achieved under the same chromatographic conditions for each detection method. As a result, CAD generated nearly uniform responses compared with UV detection and ELSD. It showed the best accuracy and LOD among 3 detectors and had similar precision with UV detection at higher concentrations while UV detection showed a better precision at lower concentrations than did CAD or ELSD. The LOD of CAD, in fact, can be up to two times higher than that of ELSD. The UV and ELSD linearity was satisfactory at R² > 0.99, though in the case of CAD, a log–log transformation was needed. The proposed methods were also applied to the real anti-diabetic drugs and diabetes-related dietary supplements.     

HPLC-MS法鉴别唐乐舒胶囊中非法添加的格列本脲、

摘要：目的 建立唐乐舒胶囊中非法添加格列本脲、格列齐特、格列美脲成分的鉴别方法。方法 采用VP-ODS C18（250mm×2.0 mm）色谱柱；甲醇－0.2％冰醋酸（70：30）为流动相；流量：0.2ml/min；电喷雾离子化（ESI）scan方式。采用两种HPLC条件进行验证。结果 在高效液相色谱、紫外光谱、质谱中，样品分别出现与格列本脲、格列齐特、格列美脲成分一致的峰。结论 本方法简单可行，结果准确可靠，可用于唐乐舒胶囊中添加格列本脲、格列齐特、格列美脲成分的定性鉴别。     

Formulation and characterization of extruded and spheronized pellets using pectin and crosslinking agents

The aim of this study was to prepare pellets of gliclazide by extrusion spheronization process by use of two methods in situ cross linking method and interracial complexation method and to study the effect of different cross linking agents on the formed pellets. Extrusion/spheronization being an established technique for producing spherical pellets so this technique was used to prepare pellets. The gliclazide pellets prepared by extrusion-spheronization techniques and then the formed pellets were coated with pectin solution by interfacial complexation method. The effect of cross-linkers calcium chloride and aluminium chloride concentration, by in situ cross linking on properties of gliclazide pellets like swelling and drug release were studied. The formed pellets were subjected to swelling, analysis of morphology, in dissolution and vivo studies. Most of the pellets were of acceptable shape. From the results calcium chloride when coated with pectin, retarded drug release. As the concentration of calcium chloride increased, it led to slow release of the drug. This may be due to the water solubility of calcium salt, which induced cross linking with pectin. Thus pellets with calcium chloride cross linked with pectin were beneficial, because it retarded the release of the drug. Though the release from interfacial coated pellets was retarded, it was less as compared to the in situ formed pellets. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 24 h after oral administration of optimized pellets. Thus, the developed and optimized pellets were suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance. The results suggested that the in situ cross linking pellets were able to retard the release of gliclazide greater than the interfacial complexation method. Therefore, this approach has been effectively achieved.     

Comparison of uptitration of gliclazide with the addition of rosiglitazone to gliclazide in patients with type 2 diabetes inadequately controlled on half-maximal doses of a sulphonylurea

Abstract. Patients with type 2 diabetes who are inadequately controlled on a half-maximal dose of a sulphonylurea may be managed by either increasing the dose of sulphonylurea or adding another agent. In this study, 471 patients inadequately controlled (fasting plasma glucose [FPG] 7.0 and 15.0 mmol/l) on 160 mg/day gliclazide were randomised to receive either the addition of rosiglitazone (4 mg b.i.d.) or to have their gliclazide uptitrated to a maximum of 320 mg/day during a 26-week treatment period. A reduction in HbA_1c of 1.3% (p=0.0001) was observed in the combination treatment group compared to the uptitrated gliclazide group after 26 weeks. The proportion of patients who achieved an HbA_1c value <7% was also greater in this group (48% vs. 22%). FPG was reduced by 3.0 mmol/l (p=0.0001) in the rosiglitazone plus gliclazide group compared to the uptitrated gliclazide group after 26 weeks. The improved efficacy of the combination treatment was accompanied by increased incidence of signs or symptoms suggestive of hypoglycaemia compared with uptitrating the gliclazide dose (6% vs. 2%). Only 1% of patients reported severe hypoglycaemia. The combination treatment led to increases in plasma lipoproteins, and more patients experienced oedema (11% vs. 3%). A significant increase in body weight was observed in patients receiving rosiglitazone plus gliclazide versus uptitrated gliclazide (3.4 kg; p=0.0001). The addition of rosiglitazone (4 mg b.i.d.) to gliclazide (160 mg/day) was well tolerated, and significantly more effective in improving glycaemia than uptitrating gliclazide to 320 mg/day.     

Glibenclamide vs Gliclazide in Type 2 Diabetes of the Elderly

The objective of this study was to compare the effect of two sulphonylureas on the frequency of hypoglycaemic events and glycaemic control in elderly patients with Type 2 diabetes. Twenty-two untreated elderly patients were treated with glibenclamide or gliclazide in a randomized double-blind fashion. Prior to treatment, a biochemical profile, an oral glucose tolerance test, and a 2-h hyperglycaemic glucose clamp (glucose 5.4 mmol I^-zs-1 above baseline) were performed. Patients were seen regularly over 6 months to assess glycaemic control and the frequency of hypoglycaemic reactions. Hyperglycaemic clamp studies and oral glucose tolerance tests were repeated at 1 and 6 months. The area under the curve for the oral glucose tolerance test (glibenclamide: 15.5 ± 0.7; gliclazide: 14.9 ± 0.8 mmol I^?1 ((p = NS)) and the haemoglobin A1C (glibenclamide: 7.4 ± 0.2%; gliclazide: 7.9 ± 0.5% (p = NS)) were similar at 6 months. Hypoglycaemic reactions were significantly more frequent with glibenclamide than with gliclazide: 17 vs 4 (p < 0.01). Insulin sensitivity index (ml kg^?1 min^?1 pmol ^?1 × 100) was increased significantly by glibenclamide but not gliclazide (glibenclamide: 0.284 ± 0.116 (baseline) vs 0.518 ± 0.102 (6 months) (p < 0.05), gliclazide: 0.260 ± 0.048 (baseline) vs 0.358 ± 0.048 (6 months) (p = NS)). We conclude that glycaemic control was equivalent with the two drugs but the incidence of hypoglycaemic reactions was significantly greater with glibenclamide probably because this drug increases insulin sensitivity to a greater degree.     

格列齐特原发失效与SUR1基因多态性的相关性研究

目的：观察天津汉族2型糖尿病患者服用格列齐特后的药物疗效及其与磺脲类受体（SUR）1基因33外显示Ser1369Ala多态性分布的关联性.方法：选择确诊时间＜5年,最近2个月降糖药物治疗时间累计＜1周,且最近1周无任何降糖药治疗史的患者166例.空腹血糖7.8～15.0 mmol/L,体质量指数＜28 kg/m^2.给予格列齐特治疗8周,观察药物疗效.取静脉血提取DNA,Taqman荧光定量PCR法测定SUR1基因33外显子Ser1369Ala的多态性.据单核苷酸碱基多态性分为tt、cc、ct组进行药效的比较.结果：tt组患者空腹胰岛素和HOMA模型B细胞功能指数低于cc、ct组,具有tt基因型和t等位基因的患者药物失效率明显高于具有cc、ct基因型及c等位基因的患者.结论：SUR1基因33外显子Ser1369Ala的多态性与磺脲类药物的原发性失效相关,可能是由于tt基因型影响了SUR1的功能,导致胰岛素分泌减少所致.     

格列齐特片在健康人体内的药代动力学及生物等效性研究

目的研究格列齐特片在健康人体内的相对生物利用度和生物等效性。方法20名健康成年男性志愿者采用随机分组自身交叉对照试验设计,单剂量口服80mg格列齐特片后,用高效液相色谱法测定血浆中药物浓度。结果格列齐特在0.104～12.48μg/ml浓度范围内线性良好(r=0.99988),平均回收率90.125%～104.6%,日内和日间精密度(RSD)均<10.0%。试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax):(4.4±0.9)和(4.0±0.9)h;峰浓度(Cmax):(4.8±0.6)和(5.3±0.8)μg/ml;曲线下面积(AUC)0￣48h:(86±29)和(88±33)mg·L-1·h-1;AUC0￣∞:(99±45)和(103±58)mg·L-·1h-1;消除半衰期(T1/2):(13±4)和(14±5)h。以AUC0￣48h计算的受试制剂的相对生物利用度为(99±9)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。     

高效液相色谱法测定格列齐特片的含量

目的:建立HPLC法测定格列齐特片中格列齐特含量的方法。方法:色谱柱为(Scienhome-C_(18)250mm×4.6mm,5μm),流动相为甲醇-0.2%冰醋酸(6:4),流速为1.0 ml·min~(-1),检测波长为228nm。结果:格列齐特在20～140μg·ml~(-1)线性关系良好,平均回收率100.0%,RSD 0.2%。结论:该方法简便、高效,专属性强,可作为格列齐特片的质量控制。