Interaction between atorvastatin and voriconazole in rat plasma: a HPLC-MS/MS-based study / 南方医科大学学报

OBJECTIVE@#To develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma and investigate the pharmacokinetics of atorvastatin and the changes in voriconazole concentration in rats after administration.@*METHODS@#Plasma samples were collected from rats after intragastric administration of atorvastatin alone or in combination with voriconazole. The samples were treated with sodium acetate acidification, and atorvastatin and voriconazole in the plasma were extracted using a liquidliquid extraction method with methyl tert-butyl ether as the extractant. The extracts were then separated on a Thermo Hypersil Gold C18 (2.1×100 mm, 1.9 μm) column within 6 min with gradient elution using acetonitrile and water (containing 0.1% formic acid) as the mobile phase; mass spectrometry detection was achieved in selective reaction monitoring (SRM) mode under the positive ion scanning mode of heated electrospray ion source (H-ESI) and using transition mass of m/z 559.2→440.2 for atorvastatin and m/z 350→280 for voriconazole, with m/z370.2→252 for lansoprazole (the internal standard) as the quantitative ion.@*RESULTS@#The calibration curves were linear within the concentration range of 0.01-100 ng/mL (=0.9957) for atorvastatin and 0.025-100 ng/mL (=0.9966) for voriconazole. The intra-day and inter-day precisions were all less than 13%, and the recovery was between 66.50% and 82.67%; the stability of the plasma samples met the requirements of testing. The AUC of atorvastatin in rat plasma after single and combined administration was 438.78±139.61 and 927.43±204.12 h·μg·L, CLz/F was 23.89±8.14 and 10.43±2.58 L·h·kg, C was 149.62±131.10 and 159.37±36.83 μg/L, t was 5.08±1.63 and (5.58±2.11 h, and T was 0.37±0.14 and 3.60±1.52 h, respectively; AUC, CLZ/F and T of atorvastatin in rat plasma differed significantly between single and combined administration. The HPLC-MS/MS system also allowed simultaneous determination of voriconazole concentration in rat plasma after combined administration.@*CONCLUSIONS@#The HPLC-MS/MS system we established in this study is simple, rapid and sensitive and allows simultaneous determination of atorvastatin and voriconazole in rat plasma. Some pharmacokinetic parameters of atorvastatin are changed in the presence of voriconazole, and their clinical significance needs further investigation.

Practical Exploration of Introducing PCNE Classification System to Develop MTM in Type 2 Diabetic Patients / 中国药房

OBJECTIVE： To introduce Pharmaceutical Care Network Europe （PCNE） classification system to develop medication therapy management （MTM）， and to investigate the application of PCNE classification system in solving drug-related problems （DRPs） in type 2 diabetic patients and the effect of it on clinical outcomes. METHODS： The patients with type 2 diabetes diagnosed in endocrinology department of our hospital from Jul. 10， 2018 to Oct. 31， 2018 were randomly divided into clinical pharmacist-led intervention （“physician-pharmacist-nurse” mode） group and control group receiving only traditional medical services （“physician-nurse” mode）. According to PCNE classification， the number of DRPs found in the pharmaceutical intervention group， the types of problems， causes， the types of interventions， acceptance for interventions and outcomes were analyzed and evaluated. Drug compliance （the highest score is 8） and HbA1c compliance （＜7％） were compared between 2 groups during hospitalization （or at the discharge） and 3 months after discharge. RESULTS： Totally 76 cases were included （40 cases in pharmaceutical intervention group and 36 cases in control group）. During hospitalization， 51 DRPs were found in the pharmaceutical intervention group， among which 42 problems were related to the effectiveness of treatment， mainly due to improper usage and dosage （23 problems）； the types of intervention was mainly aimed at the patient level （24 problems）. 38 problems received intervention （acceptance rate was 74.51％） and 32 problems （62.75％） were completely solved. Compared with those at admission， after following up for 3 months patients with low score （6 points） in the drug compliance of the pharmaceutical intervention group decreased from 26 to 8 （P＜0.000 1）， patients with medium score （6-8 points） increased from 10 to 22 （P＝0.006 2）， patients with high score （8 points） increased from 4 to 10， and drug compliance improved significantly， while there was no significant change in drug compliance in the control group. Compared with those at the discharge， after 3 months’ follow-up， the HbA1c compliance rate of the pharmaceutical intervention group increased from 25.00％ to 77.50％， and that of the control group increased from 25.00％ to 55.56％. There were statistical differences （P＜0.000 1）， and HbA1c compliance rate of the pharmaceutical intervention group was significantly higher than that of the control group. CONCLUSIONS： In the practice of MTM service， clinical pharmacists use PCNE classification system to collect， analyze， intervene， solve and evaluate DRPs systematically. The service mode can provide reference for standardizing pharmaceutical care mode.

Compound Huang Gan delays chronic renal failure after 5/6 nephrectomy in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms.</p><p><b>METHODS</b>High-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>The major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P(P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P(P<0.05) in rats following nephrectomy.</p><p><b>CONCLUSIONS</b>Compound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.</p>

Preparation of Mitomycin for Injection Nanoparticles by Microfluidization and Its Hemolytic Test / 中国药房

OBJECTIVE: To prepare Mitomycin C for injection-Polybutylcyanoacrylate Nanoparticles (MMC-PBCA-NPs) freeze drying preparation by microfluidization and to investigate its hemolytic feature. METHODS: The crude emulsion of MMC-PBCA-NPs was prepared by emulsion polymerization method, from which MMC-PBCA-NPs solution was prepared by microfluidization method; the encapsulation efficiency (EE) and the drug loading (DD) of the preparation were detected by ultraviolet spectrophotometry. The particle size and appearances of which were observed. A hemolytic test was performed on rabbits to observe the blood reaction of the preparation. RESULTS: The prepared MMC-PBCA-NPs freeze drying preparation was uniformly distributed and in round shape, with EE, DD and mean diameter at (85.1?3.8)%, (7.0?0.2)% and (113.5?3.86)nm, respectively. The hemolytic test was negative. CONCLUSION: It is feasible to prepare MMC-PBCA-NPs by microfluidization method.

Determination of Microelement Manganese in Changtong Oral Liquid by Atomic Absorption Spectrometry / 中国药房

OBJECTIVE:To establish atomic absorption spectrometry for the assaying of the microelement manganese in Changtong oral liquid.METHODS:The light source was hollow-cathode lamp with wavelength at 279.5nm,the electric current of the light was 3.0mA,the slit-width was 1.2nm,the air flow rate was 5.0L/min and the flow rate of acetylene was 1.0L/min.RESULTS:The calibration curves was in linear correlation with adsorption when the detection concentration range of manganese was 0.5～2.5?g/ml(r=0.9 997),the average recovery was 99.24%(RSD=2.06%,n=5).CONCLUSION:This method is simple,fast,accurate,sensitive and precise.

Preparation of antisense oligodeoxynucleotides-loaded butylcyanoacrylate nanoparticles by interfacial polymerization and their stability / 第三军医大学学报

Objective To optimize the preparation of nanoparticles encapsulating antisense oligodeoxynucleotides in a-butyleyanoacrylate carrier (ASODN in NP) and investigate their stability. Methods ASODN in NP were prepared by interfacial polymerization of butyleyanoacrylate (BCA). The formulation and technology of the prepared NP was optimized by using orthogonal design based on the single-factor experiment. The morphology of NP was examined by transmission electron microscope; The size and size distribution of NP were determined by Malvern laser granularity equipment;The encapsulation efficiency and drug loading were determined by HPLC; The ability of protecting oligodeoxynucleotides from serum was investigated on a 20% polyacrylamide-7 Murea sequencing gel (PAGE). Results The nanoparticles in the optimal conditions were of regular spherical surface and discrete. The average size was 97.1 nm,the average encapsulation efficiency and drug loading of ASODN in NP were 96.7% and 10.1% respectively; The oligonucleotides were more efficiently protected from degradation by nucleases than by oligonucleotides adsorbed into nanospheres.Conclusion ASODN in NP has good stability,encapsulation efficiency,drug loading and great potential for ASODN delivery.

Effect of skin condition on the permeability of theophylline via rat skin / 中国药理学通报

Aim To investigate the influence of skin layers ( st ratum corneum and viable layer) on the percutaneous absorption of drug with or w ithout isopropyl myristate (IPM). Methods We chose theophylline (TP ) as a model drug. Patches containing saturated concentration of TP were prepare d. The in vitrotransdermal permeation experiment via different rat skin lay ers was carried out. Results The Kp of TP via stripped skin was 2.1 times larger than that via intact skin. The permea bility was en hanced when coexisted with IPM either via intact skin or via stripped skin. Conclusion IPM can significantly enhance the percutaneous absorption of TP via different skin layers. And these data and methods represent a novel appr oach to evaluate the effects of skin damage and skin disease on drug percutaneou s absorption.

Identification of proteins and polypeptides from Fructus Lycii by HPCE / 中国药学杂志

BJECTIVE　To identify the fruits of Lycium barbarum L.(LB) and Lycium chinense Mill.(LC).METHODS　The proteins and polypeptides from the fruits of LB and LC were analysed by high-performance capillary electrophoresis.RESULTS　LB could be distinguished from LC by their electrophorograms.CONCLUSION　HPCE could be used for the pharmacognostic identification of Fructus Lycii.

The Brief Discussion on the Consulting Service of Traditional Chinese Medicine / 中国药房

OBJECTIVE:To provide reference information for improving the quality of pharmaceutical service in dispensary traditional Chinese medicine(TCM)in hospitals.METHODS:The actual and present situation of consulting service in tradi-tional Chinese medicine were summarized and analyzed.RESULTS&CONCLUSION:The consulting service in TCM is not carried out in most hospitals in China.Dispensary TCM should establish perfect consulting service system to improve the quality of pharmaceutical service.

Study on Mechanism of Action of Compound Huanggan Granules on the Kidney / 中国药房

OBJECTIVE:To research the mechanism of action of compound Huanggan gr anules(FHG) METHODS:To observe the effect of FHG on the renal blood flow and glomerular filtration rate,and its mechanism of diuresis by means of isotopic tracer,electromagnetic flowmeter and ureter catheterization RESULTS:FHG could significantly increase the renal blood flow and glomerular filtration rate,and enhance the diuresis CONCLUSION:Its diuresis is based on the increase of rena l blood flow and glomerular filtration rate,which results in the decrease of ne phrotoxic substances such as blood urea nitrogen and serum creatinine

Determination of Heavy Metal Cadmium in Changtong Oral Liquid by Inductively Coupled Plasma Mass Spectrometry / 中药新药与临床药理

Objective To determine the content of the heavy metal Cadmium(Cd)in Changtong oral liquid.Methods Inductively coupled plasma mass spectrometry(ICP -MS )was used.Results The calibration curve was linear in t he range of 0.0025～0.0125?g /mL for Cd(r=0.9997).The average recovery of the heavy me tal element of Cd was99.37%(n=5,RSD =2.73%).Conclusion This method is simple,accurate and e ffective.It can be used for the quality control of Changtong oral li quid.

Determination of ferulic acid and rhein in Shengfaling Tincture by HPCE / 中成药

AIM: To determine the content of ferulic acid and rhein in Shengfaling Tincture(Radix Angelicae Sinensis,Flos Carthami,Radix Polygoni Multiflori,ect.). METHODS:HPCE was used.The best condition was obtained with a fuse dsilca capillary tube (60 cm?75 ?m,effective length of 53 cm),30 mmol?L -1 sodium tetraborate electrophoretic buffer(pH 8.2),at a constant voltage of 12 kV and temperature at 25 ?C .The UV detection wavelength was at 313 nm and caffeic acid was adopted as internal standard. RESULTS:The calibration curves was linear in the range of 2.4-12 ?g?mL -1 for ferulic acid(r=0.999 7) and 1.6-8 ?g?mL -1 for rhein (r= 0.999 6 ),respectively.The average recovery of ferulic acid was 99.06% and that of rhein was 98.94%. CONCLUSION: This method is simple,quick and sensitive.

Effect of Changtong Oral Liquid on TGF - ?1 Expression in Intestinal Wall of Rats with Postoperative Intestinal Adhesion / 中国药房

OBJECTIVE: To observe the preventive mechanism of Changtong oral liquid on postoperative intestinal adhesion .METHODS: The intestinal adhesion model was established by traumatizing cecal scrosa and ligating adjacent abdominal wall/The effect of Changlong oral liquid on the expression of TGF-?1 was examined by immunohistochemical method.RESULTS & CONCLUSION:Changtong oral liquid can decrease the expression of TGF - ?1 of rats with adhesion .Maybe it is one of the mechanism that Changtong oral liquid can prevent postoperative intestinal adhesion.