Determination of dezocine and pethidine in human hair by UPLC-MS/MS / 中国药科大学学报

@#A rapid analytical method for the determination of dezocine and pethidine in hair samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.After cleaned hair was extracted by grinding with methanol and ultrasonic, the final solution was analyzed by UPLC-MS/MS.The targets were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 0.1% formic acid-water and methanol as mobile phase at a flow rate of 0.4 mL/min.The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of dezocine and pethidine.Dezocine and pethidine showed good linearity in the range of 0.01-8 ng/mg, with the limit of detection of 0.005 ng/mg and the LOQs of 0.01 ng/mg.The accuracy, precision, matrix effect, extraction recovery, and stability all met the requirements.The established method is simple, rapid, and accurate for the qualitative and quantitative determination of dezocine and pethidine in hair, which can be applied in the case analysis of dezocine and/or pethidine abuse.

Precise resection and defect repair of external nose malignant tumor / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the methods for the accurate resection of malignant tumors of the external nose, and the accurate evaluation and repair of tissue defects. Methods: We collected 48 cases with nasal malignant tumors treated in 980 Hospital, Joint Support Force of the People's Liberation Army from January 2010 to June 2020, including 28 males and 20 females, aged 36-86 years. The pathological types of tumors included basal cell carcinomas (n=29), squamous cell carcinomas (n=11), trichilemmal carcinomas(n=6), denoid cystic carcinoma (n=1) and non-Hodgkin lymphoma (n=1). Tumor resection was mainly based on the traditional extended resection determined by the safety margin, and Mohs surgery was used to minimize the scope of resection, for the margin that significantly affected the repairing results, such as the lesion adjacent to the nasal alar margin, nasal columella or deep easy-penetrating margin. All cases obtained tumor resection and primary/secondary defect reconstruction. Results: According to the pathological type and tumor size, the safe resection margin was mainly 4-10 mm, and Mohs surgery was used in 24 cases. Limited-size defects in 38 cases were repaired with double-leaf flaps, kite flaps, nasal dorsum brow flaps, nasolabial flaps or free tissues. Among 10 cases with compound defects, 8 cases were repaired with frontal flaps, including 4 cases with single frontal flaps, 2 cases with additional titanium mesh stent reconstruction and 2 cases with over and out frontal flaps. During follow-up of 1 to 10 years, all the flaps survived without flap necrosis, and the postoperative nasal contour and ventilation were satisfactory. One patient had tumor recurrence 18 months after operation, 2 patients died of cardiovascular and cerebrovascular diseases, and other patients survived without tumors. Conclusions: Mohs surgery can basically meet the requirements for precise resection of external nasal malignant tumors. Individualized application of adjacent tissue flaps and various frontal flaps is a reasonable choice to achieve the satisfactory outcome of external nasal repair and to take into account the complexity of operation.

Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRAS

Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health. Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying 80% of all lung cancer subtypes. Except for other mutations (

Content Determination of Potential Genotoxic Impurity Maleic Hydrazide in Azintamide / 中国药房

OBJECTIVE：To establish a method for the content determination of potential genotoxic impurity maleic hydrazide in azintamide raw material. METHODS ：HPLC-FLD method was adopted. The determination was performed on Thermo Syncronis C18 column with mobile phase consisted of 0.2 mol/L acetic acid-methanol （gradient elution ）. The column temperature was set at 30 ℃，the excitation wavelength was 315 nm and emission wavelength was 389 nm. The flow rate was 1 mL/min，and the sample size was 20 μL. RESULTS：The blank solvent and azintamide did not interfere with the determination of maleic hydrazide. The linear range of maleic hydrazide was 19.5-300 ng/mL（r＝0.999 9）. The limit of detection was 4.5 ng/mL and the limit of quantification was 19.5 ng/mL. The recovery ranged from 98.79％ to 103.76％（RSDs were lower than 3.00％，n＝9）. RSDs of precision and stability （24 h）tests were no more than 5.63％，and those of durability tests were less than 2.00％（n＝6）. Maleic hydrazide was not detected in 3 batches of azinamide raw material. CONCLUSIONS ：The method is specific ，sensitive and accurate. It can be used for the trace determination of maleic hydrazide in azintamide or other matrix.

\Quantitative determination of 10 illicit drugs in wastewater by liquid-liquid extraction-ultra performance liquid chromatography-tandem mass spectrometry / 中国药科大学学报

@#A deuterated internal standard quantitative analysis method based on liquid-liquid extraction-ultra performance liquid chromatography-tandem mass spectrometry (LLE-UPLC-MS/MS) for simultaneous determination of 10 illicit drugs in wastewater was established.Wastewater samples were concentrated by liquid-liquid extraction with dichloromethane: ethyl acetate (1∶1), and separated by a linear gradient of 0.1% formic acid-5 mmol/L ammonium formate aqueous solution and acetonitrile on a C18 column. The samples were then detected by ESI positive ion mode and multiple reaction monitoring mode (MRM) for quantitative analysis.All analytes had a good linear relationship (r ≥ 0.995 7) within the range of their respective standard curves; the limit of quantification was 1 ng/L (except amphetamine at 2.5 ng/L); the relative recovery rate ranged from 96.36% to 106.43%, and the intra- and inter-day precisions were less than 4.70%.This method is accurate, reliable and reproducible, and is suitable for the quantitative determination of 10 illicit drugs in wastewater.It is also suitable for wastewater with complex matrixes that affect solid phase extraction and enrichment.It provides a new analytical method for real-time monitoring of drug abuse.

Automatic analytical approach for the determination of 12 illicit drugs and nicotine metabolites in wastewater using on-line SPE-UHPLC-MS/MS / 药物分析学报

In this study,we developed a novel on-line solid phase extraction (SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)-based analytical method for simulta-neously quantifying 12 illicit drugs and metabolites (methamphetamine,amphetamine,morphine,co-deine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone) and cotinine(COT) in wastewater samples.The analysis was performed by loading 2 mL of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step (5％ methanol) to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection (LOD) and limit of quantification (LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and 250 ng/L,except for that of COT.The intra-and inter-day precisions were ＜10.45％ and 25.64％,respec-tively,and the relative recovery ranged from 83.74％ to 162.26％.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental re-suits of identical samples analyzed using off-line SPE.The difference rate was between 19.91％and-20.44％,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.

Free rectus abdominis myocutaneous flap for the reconstruction of major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinomas / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the method and plausibility of using free rectus abdominis flap (FRAF) to reconstruct the major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinoma. Methods: From 2007 to 2018 at No. 980 Hospital of Joint Logistic Supportive Force of People's Liberation Army of China, 13 patients with advanced carcinoma of nasal cavity and paranasal sinuses, including 11 males and 2 females, aged from 33 to 67 years, were treated with FRAF to repair the invasion of skull base, face and orbit. Based on adequate and meticulous preoperative evaluations on patients and tumors, complete resection of tumor bulks was performed. According to the sites, characters and extents of the defects, FRAF was introduced in different ways into reconstruction of major and complex defects in the craniofacial regions after resection of advanced sinonasal carcinomas, restoring the structure and contour of the craniofacial region. Results: Complete resection of tumors was achieved in all cases. For repairing the major and complex defects resulted from tumor ablation, FRAF graft was conducted in 13 patients with advanced sinonasal carcinomas. The recipient vessels were facial artery and vein in 9 cases, superficial temporal artery and vein in 4 cases. Vascular bridging with the external jugular vein was carried out in 2 cases who underwent submandibular neck dissections, in which facial artery and vein were used as recipient vessels. Free fibular flap was used along with FRAF in a case undergone bilateral maxillectomy. Pedicled galea capitis and periosteal flap were applied simultaneously in 3 cases with dura defects at the skullbase resulted from tumor resection. All flaps used in 13 cases survived uneventfully without major complications, with successful repair of defects, reconstruction of structures and restoration of contour of craniofacial regions. Conclusion: With adequate evaluation of resectability of tumors as well as nature and extent of defects after tumor removal, FRAF transplantation is an ideal method and strategy of choice for reconstructing the major and complex defects in craniofacial regions resulted from tumor ablation of advanced sinonasal carcinomas.

Research advances of fentanyl and fentanyl-related substances / 中国药科大学学报

@#Fentanyl and fentanyl-related substances are a series of synthetic and powerful anesthetics represented by fentanyl. In recent years,the abuse and trafficking of these substances in many countries around the world are serious which poses a great threat to people"s health and social stability. This paper focuses on the abuse,pharmacological and toxicological action,detection methods and control of fentanyl and fentanyl-related substances and aims to enhance people"s understanding of their basic properties,current research and control so as to provide references for future research.

Determination of plasma protein binding of peptide drug candidates by dextran-coated charcoal / 中国药科大学学报

@#The conventional equilibrium dialysis and ultrafiltration methods cannot be used to determine the protein binding of some peptides because of their non-specific adsorption on the semipermeable membrane or poor stability in the plasma. The method of dextran-coated charcoal adsorption combined with LC-MS/MS were used. Based on the kinetic principle of initial rate of candidate drugs absorbed to dextran-coated charcoal, seven phosphorylated peptides with the same amino acid sequence and different configurations in rat plasma were selected as the study model using; the protein binding in rat plasma were determined; the amino acid distribution rules affecting the changes in protein binding rates of peptide candidate drugs were summarized. The results suggest that the dextran charcoal adsorption method, as a supplementary method for the determination of plasma protein binding, is suitable for peptides or organic drug candidates that cannot be determined by traditional techniques.

Simultaneous determination of illicit drugs and their metabolites in wastewater by SPE-UPLC-MS/MS / 中国药科大学学报

@#A quantitative analysis method based on solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) for simultaneous determination of illicit drugs and their metabolites in wastewater was established. Samples filtered at pH of 2 and spiked with internal standard were loaded to Oasis Prime MCX cartridges for solid-phase extraction. The samples were washed with 4 mL of methanol and eluted with 4 mL of 5% ammonia in acetonitrile before reconstituting with 0.1% formic acid/water solution. ZORBAX Eclipse Plus C18 column was used for chromatography, and gradient elution was performed with 0.1% formic acid/water solution and acetonitrile as mobile phase. The samples were then detected by electrospray ionization (ESI) in positive ion mode, and multiple reaction monitoring mode (MRM) was adopted for quantitative analysis. All analytes had a good linear relationship (r ≥ 0.993 2) within the range of their respective standard curve; the limit of quantification was 1 ng/L (except amphetamine at 2.5 ng/L); the extraction recovery ranged from 82.13% to 99.96%; and the intra- and inter-day precisions were less than 9.43%. The method is accurate, reliable and reproducible, and is suitable for the quantitative determination of illicit drugs and their metabolites in wastewater and can provide an analytical method for real-time monitoring of drug abuse.

Application of three-dimensional cell model in tumor research / 中国药科大学学报

@#The three-dimensional cell model cultures different types of cells in vitro. By means of special materials or carriers, the cells can grow, migrate and differentiate in a three-dimensional environment. The three-dimensional cell model provides the cells with an in vitro environment that is close to in vivo, making the gene expression and signal exchange of the cells more physiologically relevant. This paper starts with the concept and classification of three-dimensional cell model, then summarizes the applications and progresses of three-dimensional cell model in tumor micro-environment, cancer metastasis and anti-tumor drug development in recent years. Based on the current shortcomings of the three-dimensional cell model, this paper presents the assumptions and prospects for the application of three-dimensional cell model in tumor therapy.

Application of Nrf2 activators in the treatment of Alzheimer′s disease / 中国药科大学学报

@#Alzheimer′s disease(AD)is an irreversible neurodegenerative disease. Main features in AD brains are abnormal deposition of amyloid-beta peptide(Aβ)in extracellular senile plaques(SP), intracellular neurofibrillary tangles(NFT)formed by hyperphosphorylated tau. The cause of AD is not clear. Oxidative stress is considered to be an important factor leading to the development of AD. Keap1-Nrf2-ARE signaling pathway is one of the most important defense mechanisms of antioxidant and/or electrophilic stress in the body. The activation of Keap1-Nrf2-ARE signaling pathway induces the transcription of a range of cytoprotective genes and reduces oxidative stress. This article outlines the therapeutic effect of flavonoids, phenols, carboxylic acids, esters and other Nrf2 activators on Alzheimer′s disease.

Development and validation of a novel and simple RP-HPLC method for the determination of related substances of tiopronin for injection / 中国药科大学学报

@#In this paper, a novel and simple RP-HPLC method for the determination of related substances of tiopronin for injection was described. The RP-HPLC analysis was performed on a C18 column, with acetonitrile-0. 1% phosphoric acid(8 ∶92), mobile phase in isocratic mode at a rate of 1. 0 mL/min. The photodiode array detector was set at 210 nm. Seven related substances were detected and the structures were characterized by mass spectrometry. The method showed great suitability, specificity and excellent linearity over the concentration range of 0. 3 to 50 μg/mL(r≥0. 999), and the limits of detection and quantitation were found to be 0. 10 and 0. 31 μg/mL, respectively. The accuracy of the method determined by the entire mean recovery ranged from 98. 7% to 103. 7%. The intra-and inter-day precision was satisfactory(RSD≤4. 4%)and robust(RSD≤6. 4%). And this method was successfully applied for the determination of related substances of tiopronin for injection, which revealed the retention of sulfhydryl compounds and glycine analogues on the RP-HPLC and the effect of the pH value of the mobile phase on the chromatographic behavior of the analytes.

Applications of nuclear magnetic resonance spectroscopy in the screening of new psychoactive substances / 中国药科大学学报

@#GC-MS and LC-MS are the main techniques used for the structural identification of new psychoactive substances at present. However, they are hard to give accurate structure information because of the hardly available corresponding reference standards and the quickly changing status of these compounds. This leads tremendous obstacle on the rapid identification of new psychoactive substances. Nuclear magnetic resonance spectroscopy is one of the most effective methods for structures identification. Therefore, NMR is especially suitable for the analysis and identification of new psychoactive substances even with rapid structural changes. This article summarizes the NMR applications for the structural analysis of new psychoactive substances including synthetic cannabinoids, synthetic cathinones, piperazines, phenethylamines, ketamine & phencyclidine-type substances, and fentanyls. It is found that the NMR signals of the main frame structure of each kind of the new psychoactive substances are basically the same. Hence, these frame structure NMR signals can provide scientific evidence for the rapid identification of new psychoactive substances. This article also look ahead the prospect for the application of LC-NMR and DOSY in new psychoactive substances, which provides new ideas for the screening of new psychoactive substances.

Determination of endogenous glutathione in rat plasma by a new derivative LC-MS/MS method / 中国药科大学学报

@#To develop a rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of endogenous glutathione in rat plasma. Glycyltyrosine was used as the internal standard(IS)and 4-(N-maleimido)phenyl trimethylammonium iodide(MPTA)was used as the derivation reagent. Chromatographic separation was achieved on a Zorbax HILIC PLUS column(4. 6 mm×100 mm, 3. 5 μm)and the mobile phase consisted of acetonitrile and 0. 1% formic acid(75 ∶25)pumped at a flow rate of 1. 0 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer by selected reaction monitoring(SRM)in the can meet positive ion mode. The linearity ranged from 3. 000 to 2 000 ng/mL(r=0. 997 1); and the limit of detection of glutathione in rat plasma was 10 pmol/L. Matrix effect, stability, precision and accuracy of the method met the requirements. The proposed method was proved to be selective and sensitive, which is suitable for the quantification of endogenous glutathione in rat plasma.

Determination of potential genotoxic impurity in ecabet sodium active pharma-ceutical ingredient by HPLC-MS/MS / 中国药科大学学报

To develop a sensitive analytical method for the determination of the genotoxic impurity mono ethyl ester of ecabet (Imp-I),an HPLC-MS/MS technique was employed. Imp-I was synthesized according to the previ-ous literatures. MS/MS and NMR were used to confirm the structure of Imp-I. A Thermo C18column was used for chromatographic separations. The mobile phase consisting of A:5 mmol/L ammonium acetate (pH adjusted to 3. 0 with formic acid)and B:acetonitrile,with a gradient program:0 min 50%B,4 min 50%B,12 min 80%B,16 min 80%B,16. 1 min 50%B and 20 min 50%B. The column was maintained at 40 °C throughout the analysis.All measurements were carried out with the mass spectrometer operated under the negative ESI mode. The selective reaction monitor (SRM)transition was used. Good linearity was obtained for Imp-I over the concentration range of 4 150 ng/mL with the coefficient of determination (r)of 0. 999. And the LOQ was 4 ng/mL. A rapid and sensi-tive HPLC-ESI-MS/MS method was developed for quantitative analysis of Imp-I in ecabet sodium APIs. This method can be of used for quality assurance of ecabet sodium in bulk commercial drugs.

Advances in racemization of protein amino acid / 中国药科大学学报

The presence of D-amino acid in proteins is thought to be a result of racemization of L-amino acid,which may influence the space structure and the functions of proteins and the connection to the occurence of some diseases has been demonstrated.Recently,tremendous advancement in instrumental techniques has brought the rapid development to analytical methods and detecting techniques in the research on racemization of protein amino acid.The advances in the relationship between racemizadon of protein amino acid and diseases,the influence factors on racemization of protein amino acid and the analytical techniques are reviewed in this article,and the research directions of racemization of protein amino acid are also given.

Synthesis of hydralazine-N-lactose and its metabolites in vitro / 中国药科大学学报

Hydralazine-N-lactose is a main impurity in hydralazine tablets.Hydralazine and lactose were used as raw materials,and silica gel column and preparation column of octadecylsilane bonded silica were selected to pre pare and purify hydralazine-N-lactose.Its in vitro metabolites were identified by utilizing SD rat liver microsomes.The results of samples in vitro were compared with blank group and the resulting metabolites structures were identified by LC-MS/MS.Hydrazine-N-lactose produced six main metabolites,including s-triazolo[3,4-a] phthalazine,3-methyl-s-triazolo [3,4-a] phthalazine,3-(1-hydroxy) methyl-s-triazolo [3,4-a] phthalazine,3-hydroxymethyl-s-triazolo[3,4-a] phthalazine,hydralazine and dehydro-hydralazine-N-lactose after in vitro metabolism.This study will be valuable in hydralazine-lactose conjunctions metabolism research and hydralazine formulation safety.

Study on extractables in disposable syringe materials / 中国药科大学学报

Extraction experiment of volatile compounds in disposable syringes from five manufacturers was undertaken by GC-MS with high-space injection and semi-volatile compounds were tested by GC-MS.MS detection ranged from 30 to 650 with electron ionization (EI) source.Vanillin was used as internal standard to monitor the sample pretreatment process.Liquid-liquid extraction (LLE) and solid-phase extraction (SPE) were compared to acquire a simple processing method with more extractables in syringe materials.HCl,NaOH,Tween 80 and ethanol-aqueous solution were used as extraction solvents.The method was successfully developed to determine the unknown volatile extractables and the results were used to investigate the safety of disposable syringes comprehensively.

Compatibility of pre-filled syringes with pharmaceutical products / 中国药科大学学报

@#Pre-filled syringes are becoming increasingly popular for packaging and delivering system of pharmaceutical products. However, their compatibility with biotherapeutics needs to be carefully assessed. This review highlights and makes critically review on the extractables and leachables, the safety evaluation and analytical methods related to the compatibility study.