Optimization of natural deep eutectic solvent extraction of phenylethanoid glycosides from Cistanche deserticola by response surface methodology coupled with genetic algorithm / 中国药房

OBJECTIVE To optimize the extraction technology fo r phenylethanol glycosides from Cistanche deserticola by natural deep eutectic solvents （NADESs），and to provide reference for the development and utilization of C. deserticola . METHODS The optimal NADESs was selected using total extraction efficiency of echinacoside ，acteoside and isoacteoside as indexes. Based on single factor test ，response surface methodology was used to select the optimal NADESs molar ratio ，the optimal NADESs water content ，the optimal liquid-solid ratio ；and the results were optimized by genetic algorithm . Using vitamin C （VC） as positive control ，the extraction effects of NADESs and traditional solvent （50％ methanol）were compared in respects of extraction efficiency and antioxidant activities. RESULTS The optimal extraction solution was NADES- 11 composed of 1， 4-butanediol and malonic acid. The optimal extraction technology was as follows as the molar ratio of 1，4-butanediol-malonic acid was 1 ∶ 2.5，water content of NADES- 11 was 18％，liquid-solid ratio was 30 mL/g，extraction time was 30 min and extraction temperature was 30 ℃. The extraction efficiency of NADES- 11 was significantly higher than that of 50％ methanol（P＜0.05）. IC 50 values of NADES- 11 extract（261.17 and 744.34 µg/mL）to 1，1-diphenyl-2-trinitrophenylhydrazine radical and hydroxyl radical were all lower than those of 50％ methanol extract （420.97 and 1 175.12 μg/mL）. Ascorbic acid equivalent antioxidant capacity of Δ 基金项目 内蒙古自治区科技创新引导项目（No.00120209）；内 NADES-11 extract（17.19 and 360.80 mg VC/g ）was higher 蒙古自治区自然科学基金资助项目 （No.2021MS08011）；内蒙古自治 than that of 50％ methanol extract （10.67 and 228.54 mg 区医疗卫生科技计划项目（No.202201367）；包头医学院“花蕾计划”项 VC/g）. CONCLUSIONS The optimized extraction process of 目（No.HL2021046） phenylethanol glycosides from C. deserticola using NADESs is ＊第一作者 硕士研究生。研究方向：中蒙药药效成分。E-mail： environmental，stable and feasible. dongjiani369@126.com

A carbon nanoparticle-peptide fluorescent sensor custom-made for simple and sensitive detection of trypsin / 药物分析学报

Herein, we report a novel sensor to detect trypsin using a purpose-designed fluorescein-labelled peptide with negatively charged carbon nanoparticles (CNPs) modified by acid oxidation. The fluorescence of the fluorescein-labelled peptide was quenched by CNPs. The sensor reacted with trypsin to cleave the peptide, resulting in the release of the dye moiety and a substantial increase in fluorescence intensity, which was dose-and time-dependent, and trypsin could be quantified accordingly. Correspondingly, the biosensor has led to the development of a convenient and efficient fluorescent method to measure trypsin activity, with a detection limit of 0.7μg/mL. The method allows rapid determination of trypsin activity in the normal and acute pancreatitis range, suitable for point-of-care testing. Furthermore, the applicability of the method has been demonstrated by detecting trypsin in spiked urine samples.

Compatibility of rubber stoppers for recombinant antitumor-antivirus protein injection by gas chromatography-mass spectrometry / 药物分析学报

A simple, rapid, and sensitive gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the simultaneous determination of two fatty acids, methyl hexadecanoate (MH) and methyl stearate (MS), to allow the evaluation of packaging-drug compatibility. The two migrants were quantified in selective ion-monitoring (SIM) mode, with limits of detection (LOD) of 0.0030 μg/mL and 0.0121 μg/mL. Linear calibration curves for MH and MS were obtained in the concentration ranges of 0.1011–5.0570 μg/mL and 0.2015–10.0740 μg/mL, respectively. The developed method was successfully applied to estimate the safety of the injection of recombinant antitumor-antivirus protein (RAAP). The results showed that the possible maximum daily intake was 3.0 ng and 12.1 ng for MH and MS, re-spectively. As these values were both below the permitted daily exposure, the migrants can be con-sidered as having low safety risk and do not affect the quality of the injection.

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS / 药物分析学报

Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as dif-ferent pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A=1.6 × 105C–1.3 × 103 (r=0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.

Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis / 药物分析学报

A simple method was established for the determination of β-propiolactone (BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry (GC-MS). The determination was performed on an Agilent HP-INNOWAX (30m × 0.32mm i.d., 0.25 μm) capillary column at the temperature of 80 °C. Electrospray ionization (ESI) was used by selective ion detection at m/z 42. The temperature for ESI source and inlet was set at 230 °C and 200 °C, respectively. Helium was used as the carrier gas at a flow rate of 25.1 mL/min. The total run time was 8 min. Acetonitrile and other components in the sample did not interfere with the determination of BPL. The results showed good linearity of BPL in the range of 0.50–10.01 μg/mL, with the limit of detection and the limit of quantification of 0.015 μg/mL and 0.050 μg/mL, respectively. Satisfactory precision was achieved for the current developed method. The method was applied to detect 6 batches of vaccine samples, and the results indicated that the target analyte BPL was present in three batches of unpurified samples, but was not detected in the purified samples, indicating the test samples were qualified. The established method was proved to be simple, versatile and sensitive, which can meet the requirements of quality control of BPL in human inactivated rabies vaccine.

Comparative pharmacokinetics of zolpidem tartrate in five ethnic populations of China

The objective of this study was to evaluate the difference in the pharmacokinetics of zolpidem tatrate in subjects from five Chinese ethnicities (Han, Mongolian, Uigur, Korean and Hui). Healthy subjects (10 Hans, 10 Mongolians, 10 Uigurs, 10 Koreans and 9 Huis) were recruited and each received a 10 mg tablet-dose of zolpidem tatrate. A total of 12 plasma samples were collected over a 12 h period after administration. The concentrations of zolpidem in plasma were determined by an HPLC-FLU method, after which the pharmacokinetic parameters were determined using DAS 2.0 software and analyzed by SPSS 16.0 software. After normalization by weight, no differences were noted in the pharmacokinetic parameters of zolpidem tatrate among the five ethnic groups (P>0.05). However, there were statistically significant differences between males and females for the pharmacokinetic parameters (P<0.05). The metabolism of zolpidem tatrate in males was faster than in females. Results indicate that ethnicity has no significant impact on the pharmacokinetics of zolpidem tatrate after a single oral dose in healthy Chinese subjects. However, an effect of gender on the pharmacokinetics of zolpidem tatrate can be noted.

Pharmacokinetics of doxapram injection in Chinese Han, Mongolian, Korean, Uigur and Hui healthy subjects / 中国药理学通报

Aim To investigate and compare the phar-macokinetics of doxapram injection in healthy subjects of different Chinese nationalities including Han, Mon-golian, Korean, Hui and Uigur, and the influence of gender,in order to provide instruction and help for the usage of doxapram for both clinic and remedy of battle wound. Methods An HPLC-UV method was used to determine the plasma concentration of doxapram. Fifty healthy subjects ( five males and five females of each nationality) were recruited for the study. A single dose of 50 mg doxapram was administered intravenously to the healthy subjects, and blood samples were collected at various predetermined time points. The pharmacoki-netic parameters were calculated by DAS software and were compared by SPSS 13. 0 software, in order to as-sess the influence of nationality or gender on pharmaco-kinetics of doxapram. Results The results indicated that the pharmacokinetic profile of doxapram in vivo could be described as two-compartment model. The main pharmacokinetic parameters for Han, Mongolian, Korean, Hui and Uygur were as follows: Cl ( 0. 25 ± 0. 11 ) , ( 0. 33 ± 0. 11 ) , ( 0. 27 ± 0. 07 ) , ( 0. 26 ± 0. 06) and (0. 39 ± 0. 25) L·h-1 ·kg-1 , while Cmax (1. 55 ± 0. 52 ) , ( 1. 02 ± 0. 30 ) , ( 1. 31 ± 0. 47 ) , (1. 48 ± 0. 46 ) and ( 0. 99 ± 0. 35 ) mg · L-1 . The AUC0-12. 5 , AUC0-∞ and Cmax of Chinese Han were sig-nificantly higher than those of Uigur and Mongolian ( P0. 05 ) . There were statistically significant differences in Vc , Vd and CL between young males and females ( P < 0. 05 ) . Conclusion The large inter-individual variation in the main pharmacoki-netics suggests the dosage of doxapram should be ad-justed for different nationalities for both clinic and rem-edy of battle wound.

Mass spectrometry technology and its application in analysis of biological samples / 药学学报

With the excellent merits of wide analytical range, high sensitivity, small sample size, fast analysis speed, good repeatability, simple operation, low mobile phase consumption, as well as its capability of simultaneous isolation and identification, etc, mass spectrometry techniques have become widely used in the area of environmental science, energy chemical industry, biological medicine, and so on. This article reviews the application of mass spectrometry technology in biological sample analysis in the latest three years with the focus on the new applications in pharmacokinetics and bioequivalence, toxicokinetics, pharmacokinetic-pharmacodynamic, population pharmacokinetics, identification and fragmentation pathways of drugs and their metabolites and metabonomics to provide references for further study of biological sample analysis.