乙酰螺旋霉素的液／液界面电化学研究

用循环伏安法研究了乙酰螺旋霉素在水／１，２－二氯乙烷界面的转移行为，论证了界面转移机制，估算了与界面转移有关的热力学参数。     

琥乙红霉素的液／液界面电化学研究

用循环伏安法（ＣＶ）研究了抗生素类药物琥乙红霉素在水／硝基苯界面的转移行为，论证了界面转移机制，计算了与界面行为有关的理论参数。     

琥乙红霉素的液/液界面电化学研究

用循环伏安法(CV)研究了抗生素类药物琥已红霉素在水/硝基苯界面的转移行为,论证了界面转移机制,计算了与界面行为有关的理化参数。     

克林霉素的液/液界面电化学研究

液/夜界面也称两不互溶电解液界面或油/水界面,液/液界面电化学是70年代中期才开始发展的电化学研究新领域,它对于模拟研究生物膜上离子转移的化学热力学和动力学基础具有积极意义。由于研究药物通过生物膜的传递过程对于认识药理和药效作用具有十分重要的作用,因此药物的液/液界面电化学研究近年来也在广泛开展。这对正确认识及模拟生物膜上的传递过程,认识药理和药效作用等有着积极的意义。     

用油/水界面伏安法测定乙酰螺旋霉素

在0.lmol/LCdCl_{22+离子在界面传递的伏安波。其特性与常规半微分极谱波类似。△ψ随乙酰螺旋霉素的浓度增加向阴极方向移动。ep乙酰螺旋霉素的浓度呈线性相关,线性范围为29～437U/m1,检测限为7U/ml。重现性的相对标准偏差为3%左右,回收率为97～102%。与生物法相比,测定样品结果的相对误差在±1%以内。}     

滴定液研究进展

目的：通过分析研究国内外滴定液发展现状,得出滴定液研究过程的重要意义,为之后滴定液的发展奠定一定基础。方法：分析总结国内外对滴定液的研究现状,比较分析《中国药典》与GB/T 601-2016中对滴定液的异同标准。结果：对滴定液的研究分析可为滴定液领域进一步发展奠定重要意义。结论：通过分析滴定液研究发展现状,对之后滴定液的深入研究存在重要意义。     

pH值对聚四氨基酞菁铜膜电化学性质的影响

目的：研究了pH值对聚四氨基酞菁铜(p—CuTAPc)膜电化学性质的影响。方法：用循环伏安法在玻碳电极上制备了p—CuTAPc膜，并用循环伏安法对其在不同酸度下的氧化还原性质进行研究。结果：发现其氧化还原电位与pH值存在线性关系，斜率为-28mV／pH。结论：质子和氢氧根离子参与了氧化还原反应。     

大鼠小肠循环液中替硝唑的差示分光光度测定法

目的：建立大鼠小肠液循环液中的替硝唑的测定方法。方法：采用差示分光光度法,测定波长为318nm和291nm,溶剂的pH分别为pH2和pH5,结果：标准曲线在4．8ug/ml-19.2ug/ml范围内呈良好的线性关系,高中低3个学度的日内RSD小于1．65％,日间RSD小于2．28％,回收率为98．6％－101．7％,结论：该法可准确测定大鼠小肠循环液中的替硝唑。     

山茱萸水提液对骨质疏松模型小鼠骨形态学影响

目的：探索山茱萸水提液防治骨质疏松症的作用机制。方法：在电子显微镜下利用电子计算机进行图象分析，观察山茱萸水提液对骨质疏松模型小鼠骨形态学影响。结论：山茱萸水提液治疗组在骨皮质厚度、骨细胞数目、骨小梁面积等方面相对空白对照组均有显著性差异，表明山茱萸水提液确实能明显改善SAM-P／6小鼠的骨质疏松状况。     

水稻在光照条件下超声强化耐受硝基苯能力实验研究

目的：通过对人工湿地特征水生生物——水稻其种子萌发及发芽的耐受硝基苯能力实验。模拟自然光照条件下观察硝基苯的先降解能力，为进一步改善松花江水质提供切实可行的污水预处理技术。方法：采用物理复合降解技术进行水稻人工模拟自然光照条件下水稻浸种、发芽的最大耐受力测定，采用L9（3^4）正交试验进行超声强化人工配水耐受硝基苯实验研究。结果：水稻对硝基苯的最大耐受力119．1mg／L．超声的最佳条件为功率100％，时间20min。结论：采用光照、超声水稻复合法具有较强降解硝基苯的能力，降解效率为64％。     

Determination of pantoprazole in human plasma by LC-MS-MS using lansoprazole as internal standard

An analytical method based on liquid chromatography with positive ion electrospray ionization (ESI) coupled to tandem mass spectrometry detection was developed for the determination of pantoprazole (CAS 102625-70-7) in human plasma using lansoprazole (CAS 103577-45-3) as the internal standard. The analyte and internal standard were extracted from the plasma samples by liquid/liquid extraction using diethyl-ether/dichloromethane (70:30; v/v) and chromatographed on a C8 analytical column. The mobile phase consisted of acetonitrile/ water/methanol (57:25:18; v/v/v) + 10 mmol/l acetic acid + 20 mmol/l ammonium acetate. The method has a chromatographic total run time of 4.5 min and was linear within the range 5.0-5,000 ng/ mL. Detection was performed on a triple quadrupole tandem mass spectrometer by Multiple Reaction Monitoring (MRM). The intra- and inter-run precisions calculated from quality control (QC) samples were 4.2 % and 3.2 %, respectively. The accuracies as determined from QC samples were -5.0 % (intra-run) and 2.0 % (inter-run). The method herein described was employed in a bioequivalence study of two tablet formulations of pantoprazole.     

Hydromorphone transfer into breast milk after intranasal administration

STUDY OBJECTIVES: To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. DESIGN: Single-dose, pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Eight lactating, nonsmoking, healthy women aged 24-32 years. INTERVENTION: Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. MEASUREMENTS AND MAIN RESULTS: Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. CONCLUSION: Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.     

Intercellular communication in cultured rabbit gastric epithelial cells.

The effects of drugs related to cyclic AMP and a tumor promoter, phorbol ester, on intercellular communications via gap junctions were investigated by the Lucifer Yellow-transfer method in cultured rabbit gastric epithelial cells. Cells were in contact with each drug for 4 hr before the microinjection of the dye into a cell. Dye transfer capacity was significantly increased by dibutyryl cyclic AMP (10(-3) M), theophylline (10(-3) M), 3-isobutyl-1-methylxanthine (10(-4) M), forskolin (10(-6) M) and irsogladine (10(-4) M); and it was inhibited by 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml). These results suggest that the intercellular communication between cultured rabbit gastric epithelial cells is upregulated by cyclic AMP.     

Isolation and identification of cyclic imide and deamidation products in heat stressed pramlintide injection drug product

This report summarizes the identification of six cyclic imide [Asu] and two deamidation products from a sample of pramlintide final drug product that had been stressed at 40 degrees C for 45 days. The pramlintide degradation products were isolated by cation exchange high-performance liquid chromatography (HPLC) followed by reversed-phase HPLC. The isolated components were characterized by mass spectrometry (MS), tandem MS (MS/MS) and when necessary, by enzymatic (thermolysin) digestion followed by liquid chromatography/mass spectrometry (LC/MS) and sequence analysis. The isolated products were identified as [Asu14]-pramlintide, [Asu21]-pramlintide, [Asu22]-pramlintide, [Asu35]-pramlintide, [1-21]-succinimide-pramlintide, and [1-22]-succinimide-pramlintide. Also identified were [Asp35]-pramlintide, the deamidation product of pramlintide at Asn35, and [Tyr37-OH]-pramlintide, the deamidation product of the pramlintide amidated C-terminal Tyr. Together these data support those presented earlier (C. Hekman et al., Isolation and identification of peptide degradation products of heat stressed pramlintide injection drug product. Pharm Res 1998;15:650-9) indicating that the primary mechanism of degradation for pramlintide in this pH 4.0 formulation is deamidation, with six of the eight possible deamidation sites observed to undergo deamidation. Gln-10 and Asn-31 are the only two residues subject to deamidation for which none is observed. The data indicate that the cyclic imide products account for approximately 20% of the total thermal degradation while the deamidation products account for 64%. The remaining degradation is due to peptide backbone hydrolysis.     

头孢曲松钠的电化学行为研究及伏安法测定

目的:研究头孢曲松钠的电化学行为。方法:用线性扫描、循环伏安及微分脉冲极谱等多种电化学手段进行测定。结果:在pH为5.0的NaAc-HAc溶液中，头孢曲松钠(ceftriaxone，简称CTRX)有两个灵敏的伏安峰，峰电流与头孢曲松钠的浓度在4.0×10~(-7)5.0×10~(-6)mol/L范围内成线性关系。用于注射剂的测定，得到满意的结果。结论:实验表明其中一个峰属于有吸附性的不可逆过程，另一为非吸附性的可逆过程，测得电极反应的电子转移数n=2。     

Nonlinear pharmacokinetics of CI-912 in adult epileptic patients

We studied the pharmacokinetics of CI-912 (1,2-benziosoxazole-3-methanesulfonamide) in 10 adults with refractory partial seizures during an open-label pilot study. Plasma and whole blood concentrations were measured by a high-performance liquid chromatograph method after a single dose and up to and at steady state with one or two dosage regimens. Steady-state clearances averaged only 42% (range 20-60%) of single-dose clearances. Vm and Km values of the Michaelis-Menten equation were calculated for 9 of the 10 patients by a new method: Vm averaged 1,272 (range 500-1,973) mg/day and Km averaged 25.1 (range 9.23-52.5) micrograms/ml. The best initial dosage for a new patient is 300 mg CI-912 every 12 h.     

新型二维液相色谱快速测定丙戊酸血药浓度的研究

目的：采用新型二维液相色谱（2D-LC-UV）建立无需衍生即可测定丙戊酸血药浓度的方法。方法：2D-LC-UV由一维和二维液相色谱系统及中间转移柱构成,样品去除蛋白后直接进样,在一维色谱柱Aston SC2（4.6 mm×25 mm,5 μm）上进行在线富集及初级分离,通过转移柱Aston SH（3.0 mm×10 mm,5 μm）捕集保留,转移到二维色谱柱Aston SCB（4.6 mm×100 mm,5 μm）上进一步分离检测。一维流动相为VCV-1D移动相（V_{20.0 mmol·L^-1磷酸铵}：V_乙腈∶V_甲醇=3∶1∶1,磷酸调pH至5.4）,流速1.0 mL·min^-1;转移柱流动相为纯水;二维流动相为OPI-1有机移动相：BPI-1碱性流动相：API-1酸性流动相=24∶40∶36（V∶V∶V）,流速1.0 mL·min^-1;柱温40℃;紫外检测波长305 nm。结果：丙戊酸在5.99~191.73 μg·mL^-1范围内与峰面积呈良好的线性关系（r=0.999 9）,可在10 min内完整出峰;方法回收率高于96%;日内、日间的精密度RSD均小于3.56%;稳定性试验RSD均小于5%。结论：本方法无需衍生、稳定性良好、简便快速、结果准确、自动化程度高,不依赖于专门的技术人员,适用于临床快速检测。     

注射用多西他赛纳米粒在犬体内的药动学研究

目的建立高通量测定犬血浆中多西他赛浓度的液相色谱-串联质谱(LC-MS/MS)方法,并将其应用于注射用多西他寒纳米粒与多西他赛注射液的药动学比较研究。方法2组Beagle犬分别前肢静脉注射5 mg·kg~(-1)的注射用多西他赛纳米粒和多西他赛注射液后,后肢静脉取血约0.5 mL。血浆样品及内标紫杉醇置于96孔板中,采用8道移液器取液进行高通量的液液萃取。采用LC-MS/MS法测定血药浓度,计算主要药动学参数。结果多西他赛的线性范围为1～500μg·L~(-1),最低定量限为1μg·L~(-1),提取回收率均大于95%,批内、批问精密度(RSD)均小于15%。注射用多西他赛纳米粒和多西他赛注射液,t_(1/2)分别为(5.3±s 1.4)和(3.2±1.4)h,MRT分别为(3.2±1.3)和(0.66±0.21)h,V_(ss)分别为(83±48)和(15±6)L,且2种制剂的t_(1/2)、MRT和V_(ss)均具有显著差异。结论该方法灵敏、准确、专一、简便并且实现高通量分析,适用于多西他赛的药动学比较研究。与多西他赛注射液相比,注射用多西他赛纳米粒能控制药物释放速率,并具有较长的体内循环时间,在一定程度上控制了急性毒性,提高机体耐受性。     

Measurement of amount of fentanyl remaining in used patches: investigation of clinical factors affecting the remaining amounts in 4 patients

Although fentanyl patches (FP) designed to sustain plasma fentanyl concentrations for 3 days are used in many patients for continuous relief of moderate to severe cancer pain, there are some cases in which effective pain relief is sustained less than for 3 days, and in which plasma fentanyl concentrations rapidly decrease at the third day after the application. In this study, we measured the amount of fentanyl remaining in FP after continuous 3-days use to clarify some clinical factors that can influence the remaining amounts in 4 patients. Average estimated fentanyl-dermal transfer rates of the collected 41 patches calculated from their remaining amounts were less than nominal rates (21.2+/-3.4 cf. 25 microg/h (2.5 mg FP); 44.9+/-5.1 cf. 50 microg/h (5 mg FP)). Intra-individual variability was also observed (CV: 6.6-14.3% (2.5 mg FP), 3.9-13.3% (5 mg FP)). The present study suggests that the estimated fentanyl-dermal transfer rates are affected by fever, patients' body mass index and application sites. Although further study is necessary to elucidate factors that can influence the variability in transdermal fentanyl absorption, the approach in this study would contribute to improving appropriate usage of FP.     

Aqueous solubility of liquid monoterpenes at 293 K and relationship with calculated log P value

Aqueous solubility is often a limiting factor in any concentration-dependent process and n-octanol/water partition coefficient, usually expressed as log P, is equilibrium between surrogate of nonaqueous biophases and water phase. The aqueous solubility of seven liquid monoterpenes: (+/-)-beta-citronellol, (+/-)-linalool, linalyl acetate, (-)-alpha-pinene, (-)-beta-pinene, eucalyptol and terpinen-4-ol were experimentally determined at 293 K. The obtained aqueous solubility data correlate well with log P values calculated by ACD/Log P software.