共振光散射光谱法测定片剂中阿昔洛韦的含量

本文采用共振光散射光谱和紫外-可见光谱研究了十六烷基溴化吡啶存在下,阿昔洛韦和曙红B的相互作用.阿昔洛韦、曙红B和十六烷基溴化吡啶相互作用形成三元缔合物,导致共振光散射强度明显增大,并产生新的共振光散射峰.体系的最大散射峰位于364 nm处.在最佳实验条件下,增加的共振光散射信号与阿昔洛韦的浓度在0.4～24μg/ml呈线性关系,方法 的检测限为0.25μg/ml.将方法 用于片剂中阿昔洛韦含量的测定,并与药典法进行了比较.     

维多利亚蓝B共振光散射光谱法测定利福平

目的 建立测定痕量利福平的高灵敏共振瑞利散射法.方法 在弱碱性Tris-盐酸缓冲介质中,维多利亚蓝B与利福平反应后生成的络合物能使共振瑞利散射显著增强,在345nm处,增强的共振光散射强度△IRRS与一定浓度范围的利福平线性相关.结果 在345nm处,利福平的质量浓度在0.016～0.83mg/L范围内与△IRRS成正比,方法的检出限(3Sb/S)为0.0029mg/L.结论 本方法用于尿样及市售利福平药物中利福平含量的测定,RSD小于1.2％,样品加标回收率为98.5％100.6％,结果满意.     

人输注静注人免疫球蛋白后对TP-ELISA法检测梅毒的干扰因素初探

目的初步探讨当静注人免疫球蛋白(p H=4)注入人体后对梅毒螺旋体酶联免疫吸附试验(TP-ELISA)检测结果的干扰。方法采用氢氧化钠调节静注人免疫球蛋白p H值;用0.9%氯化钠注射液和阴性血浆(经梅毒检测阴性的健康献浆员新鲜混合血浆)稀释静注人免疫球蛋白成不同浓度后,进行PAEG电泳和TPELISA。结果稀释后静注人免疫球蛋白的分子结构无明显差异;静注人免疫球蛋白浓度为5%,p H值7.0左右时梅毒显阳性、p H值4.0左右时梅毒显阴性;随着稀释倍数增加,蛋白浓度和p H值均有改变,梅毒结果先显阳性后转为阴性。结论静注人免疫球蛋白样品的p H值对TP-ELISA检测梅毒的结果有明显的干扰作用,静注人免疫球蛋白浓度是主要干扰因素。     

A validated RP-HPLC method for quantitative determination of related impurities of ursodeoxycholic acid (API) by refractive index detection

An isocratic RP-HPLC method was developed and validated for quantitative determination of ursodeoxycholic acid (UDCA) and its related impurities. Considering the lower molecular absorptivity of UDCA, refractive index detector was used to detect the impurities on a Phenomenex Luna C(18), 150 mm × 4.6 mm, 5 μm column. The mobile phase was 0.1% acetic acid/methanol (30:70, v/v) and flow rate was 0.8 ml/min. The detector and column temperature was maintained at 40°C. The method is linear over a range of 0.25-3.5 μg/ml for all impurities and coefficient of correlation (r(2)) was ≥0.9945. The accuracy of method demonstrated at three levels in the range of 50-150% of the specification limit and recoveries were found to be in the range of 97.11-100.75%. The precision for all related impurities was below 3.5% R.S.D. The method was applied to commercial bulk drug sample for assay purpose.     

Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles.

Nanoparticles represent promising carriers for controlled drug delivery. This work focuses on the size and molecular mass characterization of polyalkylcyanoacrylate nanoparticles formed by anionic emulsion polymerization of butylcyanoacrylate in the presence of poloxamer 188 as a stabilizer. Three different methods were used to determine the size and size distribution of the particle populations: scanning electron microscopy (SEM), dynamic light scattering (DLS), and analytical ultracentrifugation (ANUC). SEM on freeze-dried and Au-shadowed samples showed a relatively narrow distribution of virtually spherical particles with a mean diameter of 167 nm. DLS yielded a monomodal distribution with hydrodynamic diameters around 199 nm (in the absence of additional stabilizer) or 184 nm (in the presence of 1% poloxamer 188). The size distribution determined by ANUC using sedimentation velocity analysis was somewhat more complex, the size of the most abundant particles being around 184 nm. Molar particle mass distributions centered around 2.3x10(9) g/mol. The advantages and disadvantages of the three sizing techniques are discussed.     

Simultaneous screening of the stability and dosimetry of nanoparticles dispersions for in vitro toxicological studies with static multiple light scattering technique

To evaluate the nanoparticle (NP) toxicity, much efforts have been devoted for developing methods to accurately disperse NPs into aqueous suspensions prior to in vitro toxicological studies. As NP toxicity is strongly dependent on their physicochemical properties, NP characterization is a key step for any in vitro toxicological study. This study demonstrates that the static multiple light scattering (SMLS) technique allows for the simultaneous screening of the NP size, agglomeration state, stability and dosimetry in biological media. Batch dispersions of TiO₂ P25 NPs in water with various bovine serum albumin (BSA) mass fractions (from 0% to 0.5%) and dilutions of these dispersions into cell culture media were characterized with SMLS. In the batch dispersions, TiO₂ NPs are stable and well dispersed for BSA mass fraction lower than 0.2% while agglomeration and rapid settling is observed for higher BSA mass fractions. Paradoxically, when diluted in cell culture media, TiO₂ NPs are well dispersed and stable for BSA mass fractions higher than 0.2%. The TiO₂ NP dosimetry of these dilutions was evaluated experimentally with SMLS and confronted with numerical approaches. The TiO₂ NP bottom concentration evolves far more slowly in the case of the higher BSA mass fraction. Such measurements give valuable insights on the NP fate and transport in biological media to obtain in fine reliable size and dose-cytotoxicity responses.     

RP-HPLC法测定注射用胸腺法新中有关物质的含量

目的：建立以反相高效液相色谱法（RP-HPLC）测定注射用胸腺法新有关物质的方法研究。方法将样品用磷酸盐缓冲液（PBS）溶解后进行色谱分析,采用Agilent ZORBAX SB-C18（250.0 mm×4.6 mm,5μm）色谱柱,以流动相A[乙腈-水-磷酸（140∶860∶1）]和流动相B[乙腈-水-磷酸（250∶750∶1）]进行梯度洗脱,流速为1.0 mL/min,柱温40℃,检测波长210 nm,进样量20μL。结果 RP-HPLC法专属性强,重现性好,稳定性佳;有关物质在0.7098～23.6150μg/mL范围内与峰面积有良好的线性关系（r=0.9993）。结论 RP-HPLC法简单、准确、可靠,可用于测定注射用胸腺法新中有关物质的含量。     

静注人免疫球蛋白治疗新型冠状病毒肺炎的Meta分析

目的   通过Meta分析明确静注人免疫球蛋白（human immunoglobulin for intravenous injection,IVIG）对于新型冠状病毒肺炎（COVID-19）的疗效和安全性。方法 计算机检索Cochrane图书馆、PubMed、中国期刊全文数据库、中国生物医学文献数据库自2020年1月1日至2021年7月31日发表的关于IVIG治疗COVID-19的中、英文随机对照试验及队列研究。根据Cochrane系统评价员手册进行质量评价,采用RevMan 5.3软件进行Meta分析。结果 共纳入11个符合标准的临床研究,包含4个随机对照试验和7个队列研究。Meta分析结果发现：IVIG能显著降低危重型COVID-19患者的死亡率〔相对危险度（RR）=0.67,95%置信区间（CI）：0.52~0.85,P=0.001,I²=7%〕;在重型患者中,IVIG也能带来潜在的生存率改善,但差异无统计学意义〔RR=0.78,95% CI：0.52~1.18,P=0.24,I²=49%〕。IVIG在COVID-19患者中的不良反应发生率在0.0%~5.9%之间,以轻至中度不良反应为主,表现为心悸、头晕、皮疹、注射部位水肿等。结论   IVIG安全性良好,能显著提高危重型COVID-19患者生存率。在重型患者中需进一步探索IVIG的使用时机和推荐剂量,以更好地指导临床治疗。     

Comparison of electrospray ionization mass spectrometry and evaporative light scattering detections for the determination of Poloxamer 188 in itraconazole injectable formulation

A high performance liquid chromatography (HPLC) method for Poloxamer 188 using size-exclusion chromatography (SEC) was developed and two different detection mechanisms, evaporative light scattering (ELSD) and electrospray ionization mass spectrometry (ESI-MS), were compared for their quantification capabilities in itraconazole formulation. Both detection techniques coupled with SEC separation were highly effective for the determination of Poloxamer 188, which is difficult to analyze by other common HPLC methods. As expected, ESI-MS detection provided sensitivity and selectivity superior to ELSD. But since the analyte is an excipient in the formulation, high sensitivity was not required and ELSD's simplicity and ruggedness made it more appropriate for routine analysis of this formulation.     

电感耦合等离子体质谱法测定注射用美罗培南中的13个元素杂质

摘要：目的 建立电感耦合等离子体质谱(ICP-MS)法测定注射用美罗培南中Li、V、Co、Ni、Cu、Zn、As、Rh、Pd、Cd、Sb、Hg和Pb共13个元素杂质含量。方法 供试品经直接稀释后采用ICP-MS法对13个金属元素进行分析测定。以 Be、Ge、In、Bi元素为内标校正基体效应和漂移。结果 13个元素在各自的检测浓度范围内线性关系良好(r≥0.9997);各浓度点平均回收率为89.2%~114.5%(n=3);重复性为2.3%~4.6%(n=6),中间精密度为2.9%~5.7%(n=12),均满足USP 43<233>方法学验证的要求。不同厂家的注射用美罗培南中13种元素杂质含量均符合ICH规定。结论 本方法操作简单、分析速度快,准确性好、灵敏度高,可用于注射用美罗培南中元素杂质的质量控制。     

Development and validation of a novel LC non-derivatization method for the determination of amikacin in pharmaceuticals based on evaporative light scattering detection

A novel method for the direct determination of the aminoglycoside antibiotic amikacin and its precursor component kanamycin was developed and validated, based on reversed phase LC with evaporative light scattering detector (ELSD). ELSD response to amikacin was found to be enhanced by: (a) use of ion-pairing acidic reagents of increased molecular mass, (b) increase of mobile phase volatility and (c) decrease of peak width and asymmetry (obtained by controlling the mobile phase acidity and/or ratio of organic solvent to water). Utilizing a Thermo Hypersil BetaBasic C₁₈ column, the selected optimized mobile phase was water–methanol (60:40, v/v), containing 3.0 ml l⁻¹ nonafluoropentanoic acid (18.2 mM) (isocratic elution with flow rate of 1.0 ml min⁻¹). ELSD experimental parameters were: nitrogen pressure 3.5 bar, evaporation temperature 50 °C, and gain 11. Amikacin was eluted at 8.6 min and kanamycin at 10.4 min with a resolution of 1.5. Logarithmic calibration curves were obtained from 7 to 77 μg ml⁻¹ (r > 0.9995) for amikacin and 8 to 105 μg ml⁻¹ (r > 0.998) for kanamycin, with a LOD equal to 2.2 and 2.5 μg ml⁻¹, respectively.

In amikacin sulfate pharmaceutical raw materials, the simultaneous determination of sulfate (t_R = 2.3 min, LOD = 1.8 μg ml⁻¹, range 5–40 μg ml⁻¹, %R.S.D. = 1.1, r > 0.9997), kanamycin and amikacin was feasible. No significant difference was found between the results of the developed LC–ELSD method and those of reference methods, while the mean recovery of kanamycin from spiked samples (0.5%, w/w) was 97.3% (%R.S.D. ≤ 2.0, n = 6). Further, the developed method was applied for the determination of amikacin in pharmaceutical formulations (injection solutions) without any interference from the matrix (recovery from spiked samples ranged from 95.6 to 103.8%).     

Microemulsions for dermal drug delivery studied by dynamic light scattering: effect of interparticle interactions in oil-in-water microemulsions

Dynamic light scattering (DLS) was used to study the droplet size and the droplet interaction of o/w microemulsions (MEs) consisting of oils, a blend of a high and a low hydrophilic-lipophilic balance (HLB) surfactant, and a hydrophilic phase (propylene glycol/water). Like many MEs, these systems could not be diluted to infinite dilution without phase separation. Consequently, to allow a meaningful calculation of droplet diameter from data obtained from DLS, it is necessary to correct scattering measurements in high concentration regions for the nonideality arising from interparticle interaction. Scattering data were corrected for interparticle interaction using a suitable interaction model proposed for our systems. From the total interparticle interaction energy, coagulation time was calculated. The ratio between rapid and slow coagulation was of the order of 10(100), which is consistent with the observed stability of the MEs studied.     

Absolute molecular weight determination of hypromellose acetate succinate by size exclusion chromatography: use of a multi angle laser light scattering detector and a mixed solvent

Molecular weight distribution is an important quality attribute for hypromellose acetate succinate (HPMCAS), a pharmaceutical excipient used in spray-dried dispersions. Our previous study showed that neither relative nor universal calibration method of size exclusion chromatography (SEC) works for HPMCAS polymers. We here report our effort to develop a SEC method using a mass sensitive multi angle laser light scattering detector (MALLS) to determine molecular weight distributions of HPMCAS polymers. A solvent screen study reveals that a mixed solvent (60:40%, v/v 50 mM NaH₂PO₄ with 0.1 M NaNO₃ buffer: acetonitrile, pH* 8.0) is the best for HPMCAS-LF and MF sub-classes. Use of a mixed solvent creates a challenging condition for the method that uses refractive index detector. Therefore, we thoroughly evaluated the method performance and robustness. The mean weight average molecular weight of a polyethylene oxide standard has a 95% confidence interval of (28,443-28,793) g/mol vs. 28,700 g/mol from the Certificate of Analysis. The relative standard deviations of average molecular weights for all polymers are 3-6%. These results and the Design of Experiments study demonstrate that the method is accurate and robust.     

葡聚糖凝胶柱层析法分离测定注射用阿洛西林钠中的聚合物

目的建立一种利用葡聚糖凝胶柱分离测定注射用阿洛西林钠中聚合物的方法。方法注射用阿洛西林钠中的高分子杂质的定量测定是利用葡聚糖凝胶柱色谱法。色谱柱：XK16/40SephadexG-10,柱长：35cm;流动相A为pH7.0,0.025mol·L^-1磷酸盐缓冲液,流动相B为超纯水,流速：1.5mL·min^-1,检测波长254nm,进样量200μL。结果注射用阿洛西林钠在浓度为5.0～60mg·mL^-1的范围内与其峰面积呈良好的线性关系（r为0.9990）。结论本法用于注射用阿洛西林钠中的高分子杂质的测定,灵敏度高,准确性好。     

Optimization of selectivity in micellar chromatographic procedures for the determination of drugs in urine by direct injection

Selectivity was optimized for the determination of drugs in urine by direct injection micellar chromatography through changes in specific mobile phase parameters. The r?le of mobile phase pH and the type of surfactant used for mobile phase preparation was investigated. The retention of the urine matrix was found to be minimal between pH 5.5 and 7.5. The non-ionic surfactant, polyoxyethylene 23 lauryl ether (Brij 35), was found to be the surfactant of choice for the separation of drugs from urine. Favourable retention of both the urine background and the analyte was achieved with this surfactant. Micellar mobile phases of optimal composition were used to develop chromatographic procedures for the determination of furosemide, hydrochlorothiazide and propranolol in urine. Good accuracy (98-102% of drug recovered), precision (1-4% RSD) and linearity were obtained for all methods. Limits of detection for all drugs were adequate.     

An estimation method of the clearance for a one-compartment model of a single bolus intravenous injection by a single sampling

In clinical trials, sometimes only a single drug concentration can be measured from a patient, because of the burden on the patient. From a single concentration, we cannot generally obtain point estimates of each pharmacokinetic parameter in a patient. In this article, we propose a method to estimate the clearance using a one-compartment model of a single-bolus intravenous injection from a single concentration at a sampling point between 1.5 and 2.5 half-lives. This method requires an assumed value for the volume of distribution but is robust to misspecification. This approach is illustrated by simulated concentration data and cadralazine concentration data.     

An estimation method of the half-life for a one-compartment model of a single bolus intravenous injection by a single sampling

In clinical trials, sometimes only a single drug concentration can be measured from a patient because of the patient's burden. In this case, the sampling point is usually identical for all patients. From a single concentration, we cannot generally obtain point-estimates of each pharmacokinetic parameter. In this paper, we propose a method to estimate the half-life of a one-compartment model of a single bolus intravenous injection from a single concentration at a sampling point of or after three half-lives. We analytically show that the later the sampling point is the better estimate of the half-life we can get. This approach is illustrated by simulated concentration-data and nicorandil concentration-data. Therefore, we compared the performance of the proposed method with that of the Bayesian approach.     

薄层色谱法测定注射用氨酪酸中的有关物质及配伍稳定性

目的采用薄层色谱法测定注射用氨酪酸中的有关物质及配伍稳定性。方法以正丁醇-水-冰醋酸(5∶2∶1)为展开剂,在硅胶G薄层板上展开,用茚三酮的丙酮溶液显色后观察。结果确定了氨酪酸有关物质限度,及其与3种输液配伍的稳定性。结论该法简便、灵敏、准确,可作为注射用氨酪酸有关物质及配伍稳定性的快速测定。     

An improved method for the determination of 5‐hydroxymethylfurfural in Shenfu injection by direct analysis in real time‐quadrupole time‐of‐flight mass spectrometry

The emergence of direct analysis in real time (DART) ion source provides the great possibility for rapid analysis of hazardous substance in drugs. DART mass spectrometry (DART‐MS) enabled the conducting of a fast and non‐contact analysis of various samples, including solid or liquid ones, without complex sample preparation or chromatographic separation. In this study, a modified DART‐quadrupole time‐of‐flight mass spectrometry (DART‐QTOF‐MS) method was developed for identification and determination of 5‐hydroxymethylfurfural (5‐HMF) in Shenfu (SF) injection. The quantitative transfer of sample solution was introduced to the glass tips of DIP‐it sampler at a fixed volume, which significantly increases the repeatability and accuracy of analytical results. The protonated ion of dibutyl phthalate in the atmosphere was used as the reference mass for TOF‐MS recalibration during the data acquisition for constant high accuracy mass measurements. Finally, the developed DART‐MS method was used to determine 5‐HMF in seven batches of SF injection, and the contents of 5‐HMF were not higher than 100 µg/mL. The results obtained were further confirmed by an ultra‐high performance liquid chromatography combined with triple quadrupole mass spectrometer (UHPLC‐QQQ‐MS). The overall results demonstrated that the DART‐QTOF‐MS method could be applied as an alternative technique for rapid monitoring 5‐HMF in herbal medicine injection. Copyright © 2015 John Wiley & Sons, Ltd.