Effervescent tablet‐assisted demulsified dispersive liquid–liquid microextraction based on solidification of floating organic droplet for determination of methadone in water and biological samples prior to GC‐flame ionization and GC‐MS

A novel effervescent tablet‐assisted demulsified dispersive liquid–liquid microextraction based on the solidification of floating organic droplet was developed to determine methadone prior to gas chromatography with flame ionization detection and gas chromatography with mass spectrometry. In this method, a tablet composed of citric acid, sodium carbonate, and 1‐undecanol was utilized. The resulting effervescent tablet generated carbon dioxide in situ to disperse 1‐undecanol in the sample. Thus, the dispersive and extraction processes were performed in one synchronous step. An aliquot of acetonitrile as the demulsifier solvent was used for the separation of two phases instead of centrifugation. Under optimal conditions, the developed method was linear up to 50 000 µg/L with correlation coefficients higher than 0.99. Moreover, limits of detection and limits of the quantification were in the range of 3‐10  and 7‐30 µg/L in water and biological samples, respectively. Intra‐ and interday precisions (n = 6) of the spiked methadone at a concentration level of 50 µg/L were over ranges of 5.1‐6.8% and 5.7‐7.1%, respectively. The preconcentration factors and recovery values were obtained in the range of 140‐145 and 98.1 to 101.6% in real samples, respectively.     

毛细管区带电泳法测定复方甘草片中的甘草酸、甘草次酸、吗啡和苯甲酸钠

 在紫外检测波长为 2 2 8nm、电压为 14kV、背景电解质为 5 0mmol/L硼砂溶液、内标为氢氯噻嗪的条件下 ,用毛细管区带电泳法对复方甘草片中的甘草酸、甘草次酸、吗啡和苯甲酸钠进行了定量分析。结果甘草酸、甘草次酸、吗啡和苯甲酸钠的相对峰面积 (组分与内标的峰面积之比 )与各自的质量浓度之间呈良好的线性关系 ,上述 4种组分的平均回收率分别为 98 2 % ,97 3% ,97 1%和 97 5 %。方法简便、快速、准确。     

复方维生素B片中主要成分的高效毛细管电泳电化学法检测

采用高效毛细管电泳－电化学检测法同时测定复方维生素B片中的主要成分维生素B1，B12，B6和C的含量；研究了电极电位，运行缓冲溶液的浓度和酸度，电泳电压和进样时间等对电泳的影响，以微铂电极为工作电极，检测电位＋0．5V（vs SCE)，在pH9.0的15mmol/L Tris-1mmol/L H3BO3缓冲溶液中，上述4组分在5min内获得基线分离；维生素B1，B12，B6和C的线性范围分别为2．1mg/L-1.0g/L,6.0mg/L-0.80g/L,1.4mg/L-0.72g/L和0．97mg/L-0.44g/L检出限分别为0．50mg/L,1.0mg/L,,0.65mg/L和0．40mg/L；5次测定峰高的相对标准偏差分别为2．4％，3．0％，3．1％，和2．5％，5次测定的平均回收率分别为99％，102％，98％和100％。     

高效毛细管电泳电导法快速检测复方维生素B片中的VB1、VB12、VB6和VC

采用高效毛细管电泳电导法同时分离、测定了复方维生素B片中的主要成分VB1, VB12,VB6和VC的含量.研究了运行缓冲溶液的酸度和浓度、电泳电压、进样时间等因素对电泳的影响.在优化的实验条件下40 mmol/L Tris -4 mmol/L H3BO3 (pH 8.0) 的缓冲溶液中加入0.30 mmol/L CTAB(溴化十六烷基三甲基铵),分离电压为15 kV,上述4组分在5 min内得到良好的分离.维生素B1,B12,B6和VC的线性范围分别为5.5～1.0 mg/mL; 15～1.5 mg/mL; 1.0～0.40 mg/mL和6.6～0.80 mg/mL; 检测限分别为0.80 μg/mL, 4.0 μg/mL, 0.50 μg/mL, 2.9 μg/mL; 5次测定峰高的相对标准偏差分别为2.2%, 1.6%, 3.9%, 2.8%.5次测定的平均回收率分别为99%, 94%, 100%, 97%.     

A UPLC–MS/MS approach for simultaneous determination of eight flavonoids in rat plasma,and its application to pharmacokinetic studies of Fu‐Zhu‐Jiang‐Tang tablet in rats

The purpose of this study is to establish and validate a UPLC–MS/MS approach to determine eight flavonoids in biological samples and apply the method to pharmacokinetic study of Fu‐Zhu‐Jiang‐Tang tablet. A Waters BEH C₁₈ UPLC column was employed with methanol/0.1% formic acid–water as mobile phases. The mass analysis was carried out in a triple quadrupole mass spectrometer using multiple reaction monitoring with negative scan mode. A one‐step protein precipitation by methanol was used to extract the analytes from blood. Eight major flavonoids were selected as markers. Our results showed that calibration curves for 3′‐hydroxypuerarin, mirificin, puerarin, 3′‐methoxypuerarin, daidzin, rutin, astragalin and daidzein displayed good linear regression (r ² > 0.9986). The intra‐day and inter‐day precisions (RSD) of the eight flavonoids at high, medium and low levels were <8.03% and the bias of the accuracies ranged from −5.20 to 6.75%.The extraction recoveries of the eight flavonoids were from 91.4 to 100.5% and the matrix effects ranged from 89.8 to 103.8%. The validated approach was successfully applied to a pharmacokinetic study in Sprague–Dawley rats after oral administration of FZJT tablet. Double peaks were emerged in curves of mean plasma concentration for 3′‐methoxypuerarin, which was reported for the first time.     

人体血中吗啡浓度的GC／MS测定法

本实验采用磷酸可待因作内标，经液相萃取、乙酸酐衍生化处理后，用ＧＣ／ＭＳ的选择离子定量模型（ＳＩＭ）测定肿瘤病人体内吗啡的血药浓度。方法的最低检出限为０．９５ｎｇ／ｍＬ，在１．０～６０．０ｎｇ／ｍＬ的浓度范围内，标准曲线呈良好的线性，ｒ＞０．９９８，日内日间误差小于９．０％，回收率达９６％，已成功地应用在８例肿瘤病人口服３０ｍｇ吗啡控释片的药代动力学的研究上。     

Metabolic mapping of Schisandra sphenanthera extract and its active lignans using a metabolomic approach based on ultra high performance liquid chromatography with high‐resolution mass spectrometry

Schisandra sphenanthera , the dried ripe fruit of Schisandra sphenanthera Rehd. et Wils , is widely used as a restorative, tonic and nutrition in many countries. Wuzhi tablet, an ethanol extract preparation of Schisandra sphenanthera , is a well‐known herbal medicine widely used in China. Our previous studies show that Wuzhi tablet and its active lignans significantly protect liver injury. However, its metabolic profile remains unknown in vivo and in vitro . In this study, ultra high performance liquid chromatography coupled with electrospray ionization high‐resolution mass spectrometry based metabolomics was employed to decipher the metabolic map of Wuzhi tablet and its active lignans. Serum (2 h) and urine (24 h) samples after a 700 mg/kg single oral dose of Wuzhi tablet, and mice liver microsome samples after incubation with its active lignans were collected and analyzed. The data were further analyzed using metabolomics and metabolite identification software. In total, 33 metabolites in vivo and 34 metabolites in vitro were identified, and six among them were new metabolites. The major metabolic reactions encompassed demethylation, hydroxylation, dehydrogenation, and epoxidation. Taken together, in vitro and in vivo studies revealed the metabolic profile of Wuzhi tablet and its active lignans and demethylation and hydroxylation were their major metabolic pathways.     

三维荧光二阶校正法用于复杂基体样中川芎嗪和替米沙坦的快速定量分析

采用三维荧光光谱法,结合化学计量学中基于交替归一加权残差(ANWE)算法的二阶校正方法,实现了人血浆样品中川芎嗪和替米沙坦的同时快速定量分析.当组分数N取4时,ANWE算法解析获得的川芎嗪和替米沙坦的平均回收率分别为99.3士3.5%和96.8±2.0%.本文同时给出了此方法的检测限(LOD)与定量下限(LOQ),获得...     

Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using 1H-NMR- and MS-based metabolomics

Duzhong Jiangya Tablet (DJT) composed of Eucommia ulmoides Oliv. and several other traditional Chinese medicines is a Chinese herbal compound, which is clinically used to treat hypertension. The aim of this study was to evaluate the antihypertensive effect of DJT and amlodipine besylate (AB) on the synergistic treatment of spontaneously hypertensive rats (SHRs), and to explore its antihypertensive mechanism. The synergistic therapeutic effect of DJT in combination with AB on SHR was studied using two metabolomics methods based on mass spectrum (MS) and nuclear magnetic resonance. Metabolomics analysis of plasma, urine, liver, and kidney and the combination of orthogonal partial least squares discriminant analysis was performed to expose potential biomarkers. Then, the overall metabolic characteristics and related abnormal metabolic pathways in hypertensive rats were constructed. Blood pressure measurements showed that DJT combined with AB has better effects in treating hypertension than it being alone. A total of 30 biomarkers were identified, indicating that hypertension disrupted the balance of multiple metabolic pathways in the body, and that combined administration restored metabolite levels better than their administration alone. The changes of biomarkers revealed the synergistic therapeutic mechanism of DJT combined with AB, which provided a reference for the combination of Chinese and Western medicines.     

Precise analysis of thyroxine enantiomers in pharmaceutical formulation by mobility difference based on cyclodextrin

Identification and determination of chiral pharmaceutical residues is still a challenging analytical puzzle. In this work, a simple, rapid, and effective method for chiral D/L-tetraiodothyronine (T4) separation and quantitative was developed based on host–guest recognition using ion mobility spectrometry-mass spectrometry (IMS-MS). The D/L-T4 enantiomers were mobility separated by their diastereomeric complexes through mixing with cyclodextrin (CD) and metal ions. D/L-T4 was first separated by complexing with host molecule (α-, β-, γ-CD), observing weak peak-to-peak resolution (R_p-p) by the formed binary complex [CD + D/L-T4-H]⁺, and the R_p-p decreased with the CD size increasing. However, the separation effect of D/L-T4 was much improved with the addition of divalent metal ions (G²⁺) by the formed ternary complex [CD + D/L-T4 + G]²⁺. In comparison, α-CD related complexes can possess the best separation effect for D/L-T4 in most cases. Considering the high selectivity, non-toxic, and chemically stable of β-CD, [β-CD + D/L-T4 + Ca]²⁺ was selected for D/L-T4 analysis (R_P-P = 0.764). Whereafter, chemical theoretical conformations for [β-CD + D/L-T4 + H]⁺ and [β-CD + D/L-T4 + Ca]²⁺ were optimized, discovering similar micro-interaction modes between [β-CD + D-T4 + H]⁺ and [β-CD + L-T4 + H]⁺; while with the addition of Ca²⁺, significantly different interaction modes were observed between [β-CD + D-T4 + Ca]²⁺ and [β-CD + L-T4 + Ca]²⁺. And theoretical collision cross section (CCS) trends for the complexes were consistent with that of the experimental results. Additionally, calibration curves were linear within 1.00 to 10⁴ ng mL^?1 with coefficient (R² > 0.99), gaining the limit of detection (LODs) calculation of 0.11 ng mL^?1, and the detection range between D-T4 and L-T4 of 45.6:1 to 1:59.8. Finally, the method was applied for D/L-T4 detection in Levothyroxine tablets, the detection content has good consistency on drug labeling. Because the proposed method exhibited good analytical performance in terms of speed, selectivity, sensitivity, and reproducibility of the measurements, that can be a promising strategy for effective D/L-T4 detection in pharmaceutical industries or other practical samples.