Advances in the development of amorphous solid dispersions:The role of polymeric carriers

Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.

Preparation and Characterization of Solid Dispersions of Silymarin with Polyethylene Glycol 6000

Aim To prepare and characterize solid dispersions of silymarin with the intention of improving their dissolution properties. Methods The solid dispersions were prepared by the fusion method with polyethylene glycol 6000(PEG 6000) as the carrier. Evaluation of the properties of the dispersions was performed using dissolution studies, X ray powder diffraction and Fourier transform infrared (FT IR) spectroscopy. Results The rate of dissolution of silymarin was considerably improved as compared with pure silymarin when formulated in solid dispersions with PEG 6000. The data of the X ray diffraction showed some changes in the parameters of lattice spacing [ d ], peak position and relative intensities. FT IR together with those from X ray diffraction showed the absence of well defined drug polymer interactions. Conclusion The dissolution improvement of poorly soluble silymarin could be illuminated by the changes of the lattice parameters of PEG 6000 and the drug.

Preparation and characterisation of solid dispersions of tanshinone ⅡA, cryptotanshinone and total tanshinones

Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza Bge.Tanshinone ⅡA and cryptotanshinone are the major components in total tanshinones.However, the bioavailability of both compounds is low due to poor water solubility. To enhance the solubility and dissolution rate of tanshinone ⅡA, cryptotanshinone and total tanshinones,three common used hydrophilic carriers including PEG 6000, poloxamer 188 and PVP K30 were used to prepare the solid dispersions at different ratios, respectively. The solid dispersions were characterised by scanning electron microscopy(SEM), differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR). The results of powder X-ray diffraction confirmed the microcrystal state of total tanshinones in solid dispersions and no chemical interaction between total tanshinones and carriers was observed in FTIR spectra. The solubility and dissolution rate of tanshinone ⅡA and cryptotanshinone were significantly increased in all solid dispersions. Regarding tanshinone ⅡA, the solubility and dissolution rate of in solid dispersions prepared with poloxamer 188 were significantly higher than that with PEG 6000 and PVP K30. The higher solubility and dissolution rate of cryptotanshinone were obtained in solid dispersion of PVP K30 than that of PEG 6000 solid dispersions but no significant difference from poloxamer 188 solid dispersions. The results indicate that the superior carrier for preparation of tanshinone ⅡA and total tanshinones solid dispersions is poloxamer 188, and that for cryptotanshinone is PVP K30.

Investigating the molecular dissolution process of binary solid dispersions by molecular dynamics simulations

Dissolution molecular mechanism of solid dispersions still remains unclear despite thousands of reports about this technique. The aim of current research was to investigate the molecular dissolution mechanism of solid dispersions by molecular dynamics simulations. The formation of ibuprofen/polymer solid dispersions was modeled by the simulated annealing method. After that, the models of solid dispersions were immersed into the water box with 25–30 ? thicknesses and 50–100 ns MD simulations were performed to all systems.Simulation results showed various dissolution behaviors in different particle sizes and various polymers of solid dispersions. Small-sized particles of solid dispersions dissolved quickly in the water, while the large particles of PEG or PVP-containing solid dispersions gradually swelled in the dissolution process and drug molecules may aggregate together. In the dissolution process, the carboxylic groups of ibuprofen molecules turned its direction from polymer molecules to external water box and then the drug molecules left the polymer coils.At the same time, polymer coils gradually relaxed and became free polymer chains in the solution. In addition, solid dispersion with poloxamer could prevent the precipitate of drug molecules in the dissolution process, which is different from those of PEG or PVPcontaining systems. This research provided us clear images of dissolution process of solid dispersions at the molecular level.

Preparation and characterization of solid dispersions of Quercetin with PEG4000

Objective To enhance the solubility,quicken the speed of digesting and absorption,and increase the bioavailability of quercetin(3,3',4',5,7-pentahydroxyflavone).Methods A series of Quercetin-PEG4000 solid dispersions were prepared by fusion method.The configuration and property of solid dispersion were characterized by solubility tests,dissolution tests,FTIR spectra,differential scanning calorimetry(DSC)and microphotograph.Results 1.According to solubility tests the the mass ratio of quercetin to PEG4000 affected strongly on the solubility of solid dispersions,on the whole,the relation of the solubility of solid dispersions to the mass ratio presented linear relationship.The preparation temperature had little effect on the solubility of solid dispersions.The surface-active agent,polysorbate80 increased strongly the solubility of solid dispersions.2.According to the dissolution tests,the mass ratio of quercetin to PEG4000 affected strongly on the dissolution of solid dispersions,the preparation temperature had little effect on the dissolution of solid dispersions.The surface-active agent,polysorbate80 increased strongly the dissolution of solid dispersions,and after addition polysorbate80,the dissolution of solid dispersions was two times of the dissolution of solid dispersions without polysorbate80.3.According to the DSC results,except that a little of quercetin molecular existed as crystalline state in the solid dispersion with the mass ratio was qu:PEG=1:2,quercetin existed as amorphous phase in other mass ratio solid dispersion.4.According to the FTIR spectra and microphotograph results,the relation of quercetin and PEG4000 was mainly physical mixing in quercetin-PEG4000 solid dispersion.Quercetin was just like solute in solution,and PEG4000 was just like solvent in solution.The force between quercetin and PEG4000 was mainly hydrogen bonding,so the biological activity of quercetin would not be influenced greatly after the formation solid dispersion.Conclusions These results suggest that quercetin existed mainly as amorphous phase in solid dispersion;the solubility and the dissolution in water were increased obviously after formation the solid dispersion.

Cooperative effect of polyvinylpyrrolidone and HPMC E5 on dissolution and bioavailability of nimodipine solid dispersions and tablets

Solid dispersion(SD)systems have been extensively used to increase the dissolution and bioavailability of poorly water-soluble drugs.To circumvent the limitations of polyvinylpyrrolidone(PVP)dispersions,HPMC E5 was applied in the formulation process and scaling-up techniques,simultaneously.In this study,SD of nimodipine(NMP)and corresponding tablets were prepared through solvent method and fluid bed granulating one step technique,respectively.Discriminatory dissolution media were used to obtain reliable dissolution results.Meanwhile,the stability study of SDs was investigated with storage under high temperature and humidity conditions.Moreover,the solubility of SDs was measured to explore the effect of carriers.The preparations were characterized by DSC,PXRD,and FTIR.Dramatical improvements in the dissolution rate of NMP were achieved by the ingenious combination of the two polymers.Binary NMP/PVP/HPMC-SDs released steadily,while the dissolution of single NMP/PVP-SDs decreased rapidly in water.The fluid-bed tablets(FB-T)possessed a similar dissolution behavior to the commercial Nimotop TM tablets.The characterization patterns implied that NMP existed in an amorphous state in our SDs.Furthermore,the results of stability tests suggested a better stability of the binary SDs.A special cooperative effect of PVP and HPMC was discovered on dissolution characteristics of NMP SDs and tablets,which could be extended to other drugs henceforth.Finally,the bioavailability of FB-T was evaluated in beagle dogs with Nimotop TM as the reference,and the results showed a higher AUC 0–12h value for FB-T.

Improvement of Dissolution Rate of Gliclazide Using Solid Dispersions with Aerosil 380 and Its Effect on Alloxan Induced Diabetic Rats

The main objective of this research is to conduct a comprehensive study for enhancing the aqueous solubility of poorly water soluble gliclazide using hydrophilic fumed silica particles (Aerosil®380) and evaluating the influence of silica on drug release profile and pharmacological activity on alloxan induced diabetic rats. Solid dispersions (SD’s) of gliclazide were prepared using solvent evaporation method. The dissolution profiles and solid state characterization of the SD’s prepared were all evaluated. The dissolution rate of gliclazide in the SD’s with fumed silica (weight ratio, 1:1) was approximately 38%, which is about 10 fold higher than that of the pure drug after 30 min. After forming the SD’s, gliclazide changed into an amorphous state, which can infer from differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) also revealed the formation of weak hydrogen bonding through the interactions between the secondary amine groups of gliclazide and silanol groups of silica particles in the SD’s. The rapid dissolution rate from the SD’s might be attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. Further, we investigated the antidiabetic effects of SD’s of gliclazide in alloxan induced diabetic rats. The SD’s of gliclazide decrease the blood glucose level 64% whereas the conventional gliclazide decreases only 37% in diabetic rats. Lipid profiles, kidney and liver functions are remarkably improved in diabetic rat treated with SD’s of gliclazide than that of conventional gliclazide. These results suggest that SD’s of gliclazide have much more bioavailability and hence are more pharmacologically active than that of conventional gliclazide form.

Polymer-based nanoparticulate solid dispersions prepared by a modified electrospraying process

A modified electrospraying process is exploited to enhance the dissolution profiles of a poorly water-soluble drug. With polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix and ketoprofen (KET) as a model drug, polymer-drug composites in the form of nanoparticles were prepared and characterized. The surface morphologies, the physical status of the drug, and the drug-polymer interactions were studied using FESEM, DSC, XRD, and ATR-FTIR. FESEM observations demonstrated that the nanoparticles gradually decreased in size from 640 ± 350, to 530 ± 320, 460 ± 200 and 320 ± 160 nm as the KET content increased from 0, to 9.1%, 16.7% and 33.3% w/w, respectively. Results from DSC and XRD suggested that KET was distributed in the PVP matrix in an amorphous manner at the molecular level. This is thought to be due to their compatibility, arising through hydrogen bonding as demonstrated by ATR- FTIR spectra. In vitro dissolution tests showed that the nanoparticles released the incorporated KET within 1 min, evidencing markedly improved dissolution over pure KET and a KET-PVP physical mixture. Electrospraying can hence offer a facile route to develop new polymer composites for biomedical applications, in particular for improving dissolution rate of poorly water-soluble drugs.

Dissolution improvement by solid dispersions composed of nifedipine, Eudragit?E and silica from rice husk

Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].

Development,characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug

The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.

Physicochemical Characterization and Solubility Enhancement Studies of Mebendazole Solid Dispersions in Solvent Mixtures

Abstract： The objective was to obtain solid dispersion to improve the dissolution rate, solubility and oral absorption of MB （mebendazole）, poor water-soluble drugs. The new formulation was characterized by DSC （differential scanning calorimetry）, PXRD （powder X-ray diffraction）, FT-1R （fourier transform infrared spectroscopy） and STEM （scanning transmission electron microscopy） methods. Solid dispersions of MB with polyvinylpyrrolidone K-30 （PVP K30） were prepared by solvent evaporation method. The solubility of MB （original powder） and that of the solid dispersions was measured at 25℃ in ethanol-water. The aqueous solubility of MB was favoured by the presence of the polymer in solvent mixtures. Combination of solid dispersions with co-solvents increased the water solubility of MB in a larger extent that each method separately. Solubility parameter （o） was used to relate to solubility profiles. MB and the solid dispersions show a solubility curve with a single peak at 51 = 30.78 MPav2. Solid state characterizations indicated that the solid dispersion exist an amorphous material entrapped in polymer matrix getting highest improvement in wettability and solubility.

Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers.Thermogravimetric analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AESD.Optimal prescriptions were screened via the dissolution degree determination method.Using Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion.Acute toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for toxicity.RESULTS:AE-SD showed that AE existed in the carrier in an amorphous state.Compared with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion.Therefore,it was more suitable as a carrier material for AE-SD.The addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of PVP.The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also optimal.Based on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than AE.The results showed that the drug metabolism in AE-SD was better,and the residence time was shorter.The toxicology study showed that both AE and AE-SD had no toxicity.CONCLUSION:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,as demonstrated by in vitro dissolution experiments.In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo,providing a new concept for the research and development of AE preparations.

Exploring the potential of porous silicas as a carrier system for dissolution rate enhancement of artemether

Malaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A Results of a survey of drug-resistant malaria demonstrated safe proclivity to nearby all anti-malarial regimes accessible except from artemisinin and its derivatives. Artemether is a BCS class IV drug effective against acute and severe falciparum malaria;hence there is a strong need to improve its solubility. Silica is one of the most widely studied excipients. Silica can be used in solubility enhancement by preparing its solid solution/dispersion with the drug. The objective of this research was to improve dissolution rate of Artemether using non-precipitated porous silica(Aeroperl 300 Pharma) and precipitated silica like EXP. 9555, EXP. 9560, and EXP. 9565. Specific surface area calculated from BET method of porous silicas viz. APL 300(A), Exp. 9555(B), Exp. 9560(C), Exp. 9565(D) was found to be 294.13 m^2/g(A), 256.02 m^2/g(B), 213.62 m^2/g(C) and 207.22 m^2/g(D) respectively.The drug release from the developed formulation was found to be significantly higher as compared to neat ARM. This improved solubility and release kinetics of ARM may be attributed to high surface area, improved wettability and decreased crystallinity. Solid-state characterization of the developed optimized formulation F3 was carried out with respect to FTIR chemical imaging, XRD,SEM, and DSC. All the porous silicas which we have explored in the present context showed a significant capability as a carrier for solubility enhancement of ARM.

How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus

The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling,affecting molecular mobility,crystallinity,particle size and finally,the drug dissolution rate.As the stability of these metastable systems depend on both formulation and process variables,the aim of this study was to assess for the first time,the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil(a hydrophobic crystalline drug)and Soluplus(an amphiphilic,hygroscopic amorphous polymer).Each of these variables was tested at three levels.Scanning electron microscopy,laser diffraction and X-ray powder diffraction were used to analyze morphology,particle size distribution and crystallinity of ball milled formulations respectively.Dissolution studies were also carried out.Advanced tools of applied physics,namely solid state 1H NMR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on storage.It was shown that both tested variables determined the particle size of the formulation.When the rotational speed of 400 rpm was used,all solid dispersion were XRD-amorphous,but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was necessary.While the formulation was exposed to water vapor,the hydration level increased with an increasing polymer load as well.Hence,the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or multilayers.Such behavior may have impact on the kinetics of the amorphous drug recrystallization,and finally deteriorate its dissolution.

Preparation and evaluation of the solid dispersions of poorly soluble silybin

To improve its solubility and dissolution,solid dispersions of silybin in PVP K30 were prepared by the conventional solvent evaporation method and characterized by equilibrium solubility and dissolution studies,differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy（FTIR）.Silybin solid dispersions showed increased solubility and rates of dissolution compared with pure drug and corresponding physical mixtures of silybin and PVP K30.Thermograms of various solid dispersions did not show the melting peak of pure silybin,indicating that silybin was in amorphous form inside the polymer carrier.FTIR studies demonstrated the presence of interactions between hydroxyl groups of silybin and carbonyl groups of PVP K30 in solid dispersions.Solid dispersion techniques can be used to formulate water insoluble drugs to improve their dissolution in vitro and absorption in vivo.

The preparation and characteristics of febuxostat SiO2 solid dispersions

In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.

Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion

The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion(HME).Carbamazepine(CBZ)was selected as model drug and combinations of Kollidon VA64(VA64),Soluplus(SOL)and Eudragit EPO(EPO)were utilized as carriers.Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters,differential scanning calorimetry(DSC),hot stage microscopy and thermogravimetric analysis.Physicochemical properties of solid dispersions were determined by DSC,X-ray diffraction,fourier transform infrared spectroscopy,dissolution and accelerated stability testing.The results show that drug-polymer miscibility at temperatures below the melting point(Tm)of CBZ was improved by combining EPO with VA64 or SOL.With 30%drug loading in a solid dispersion in SOL:EPO(1:1,w/w),CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form.The dissolution rate of the solid dispersion was significantly increased(approximately 90%within 5 min)compared to either the pure drug(approximately 85%within 60 min)or the corresponding physical mixture(approximately 80%within 60 min)before and after storage.The solid dispersion in SOL:EPO(1:1,w/w)was relatively stable at 401C/75%RH under CBZ tablet packaging conditions for at least 3 months.In conclusion,polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.

Development and Evaluation of Stable Paracetamol Loaded Solid Dispersion with Enhanced Analgesic and Hepatoprotective Property

Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.

一种替米考星高效双层包衣微丸的制备

为了克服替米考星水溶性差、味苦、生物利用度低的缺陷,将固体分散技术和包合技术相结合,采用熔融喷雾法,进行了替米考星高效双层包衣微丸的制备。主药为替米考星,辅料为共聚维酮、氢化蓖麻油、β-环糊精、聚乙二醇、聚氧乙烯氢化蓖麻油、聚维酮、羟丙甲纤维素、聚丙烯酸树脂等。微丸由丸芯、速释药物衣层、掩味衣层组成。丸芯采用固体分散融熔法技术制备,替米考星以分子水平均匀分散在伴侣型复合辅料中,使生物利用度更高;速释药物衣层使释放速度更快;掩味衣层掩盖药物异味。该方法所制备的替米考星高效双层包衣微丸外观呈圆形,水溶性良好,无苦味,药代动力学试验表明口服给药体内吸收速度快、起效快、血药浓度高、疗效好。

分散固相萃取净化-超高效液相色谱-串联质谱法测定蜂蜜中双甲脒、杀虫脒及其代谢物

该研究建立了分散固相萃取-超高效液相色谱-串联质谱(dispersive solid phase extraction-ultra-performance liquid chromatography,UPLC-MS-MS)检测蜂蜜中双甲脒、杀虫脒及其代谢物残留的分析方法。蜂蜜样品2 g加入10 mL水溶液充分混匀,经1%(体积分数)氨化乙腈超声辅助提取后离心,利用N-丙基乙二胺、C18、氨基键合硅胶混合材料进行分散固相萃取净化,采用ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm)色谱柱分离,以甲醇和0.1%(体积分数)甲酸水溶液为流动相进行梯度洗脱,多反应监测模式正离子扫描分析。6种农药及其代谢物平均回收率为84.1%~113.8%,相对标准偏差为0.9%~6.0%,检出限为0.2~0.8μg/kg,定量限为0.7~2.5μg/kg。实验结果表明该方法快速简便、灵敏度高,适用于蜂蜜中双甲脒、杀虫脒及其代谢物残留同时分析。