Rapid Limit Test of Seven Pesticide Residues in Tea Based on the Combination of TLC and Raman Imaging Microscopy.

Numerous studies have shown that pesticide residues in tea exceeding the maximum residue limits (MRL) can cause harmful effects on the human body. There are many limitations in the existing analytical methods for pesticide residues in tea, so new analytical methods need to be developed. We developed a limit test method that combines thin-layer chromatography with Raman imaging microscopy (TLC-RIM). Seven residual pesticide components in tea (Avermectin, Methomyl, Carbendazim, Imidacloprid, Chlorothalonil, Azoxystrobin, and Acetamiprid) could be preliminarily separated by TLC and then irradiated by a 532 nm laser. Raman spectra of seven pesticides obtained by Raman imaging microscopy could be used to test whether the pesticide residues in tea exceed the MRL. The limits of detection of the seven pesticides were 0.04, 0.10, 0.24, 0.20, 0.12, 0.12, and 1.0 mg/mL, respectively. The simulated positive test showed that the matrix in tea did not interfere with the test of the seven pesticides. When the pesticides were tested within 8 h, the RSD of the peak heights of the seven pesticides were 1.2%~9.6%; the test results of three batches of tea showed that the imidacloprid in one batch of tea exceeded its MRL, and the results were consistent with that by UPLC-MS/MS. The TLC-RIM is fast, sensitive, stable, specific, and reliable.

Acute Oral Toxicity of Nonfluorinated Fire-Fighting Foams to Northern Bobwhite Quail (Colinus virginianus).

Long-chain per- and poly-fluoroalkyl substances (PFAS) have been the active ingredients in firefighting foams for more than 50 years. Due to their extreme persistence, regulatory agencies are concerned about their potential adverse environmental and health impacts. Recently, nonfluorinated chemical constituents have been proposed for use in fire-fighting foams in an effort to reduce the potential negative impacts of PFAS on terrestrial and aquatic flora and fauna. However, it is important to also determine the potential ecotoxicity of these nonfluorinated foam products, because we have little toxicological information for many of them. In preparation for a chronic study, we conducted an acute (24-h) oral toxicity test in northern bobwhite quail (Colinus virginianus) using six different fluorine-free foams; five were commercial foams (BioEx ECOPOL A, Fomtec Enviro USP, National Foam Avio Green KHC, National Foam NFD 20-391, and Solberg Re-Healing Foam), and one was an experimental foam (NRL 502W). A short-chain PFAS-based foam (Buckeye Platinum Plus C6) was also evaluated for comparative purposes. Groups of five birds were initially pseudogavaged with a volume of each product corresponding to a "limit" (the highest exposure concentration expected to occur environmentally). Only one bird (1 of 35) died during the limit test, indicating that all seven products have an acute median lethal dose in adult quail at or above the limit (~1500 mg/kg body wt). Environ Toxicol Chem 2022;41:2003-2007. © 2022 SETAC.

Establishment and analysis of microbial limit test methods for commonly used pediatric drugs / 上海预防医学

ObjectiveTo establish microbial limit test methods for 44 pediatric drugs. MethodsAccording to the general guidelines in Chinese Pharmacopoeia （2015 and 2020 edition， volume Ⅳ），a suitability test of the methods for 44 drugs was carried out by pour-plate method， neutralization method or dilution method. ResultsTotal aerobic microbial count： chemical oral liquid samples can be tested by 1∶10 plate method；traditional Chinese medicine need to be neutralized firstly. Then oral liquids could be tested by 1∶10 plate method and 1∶100 plate method was used for granules. Total count of molds and yeasts： all the samples can be tested by the 1∶10 plate method. The recoveries of five test strains were between 0.5 and 2.0. The specified microorganisms were all detected in the test group， while not found in the negative control group. ConclusionThe microbial limit test methods for the 44 pediatric drugs are established and the results are reliable and can be used in the quality control．

Decommissioning of oil and gas assets: industrial and environmental security management, international experience and Russian practice.

In the Russian oil and gas industry, there are still no technical regulations for unified rules and standards governing the establishment of the abandonment fund and the decommissioning of fields. With an increase in the volume of assets decommissioned, the issues of correct accounting and financial reporting of these expenses are becoming more and more urgent. There is also uncertainty regarding the taxation guidelines of operations completion on the production facilities. The strategic aspects of the decommissioning policy of oil and gas fields are stated using the example of the North Sea countries. As part of the responsible investment policy, environmental aspects and industrial safety management during decommissioning of facilities are outlined. An overview of the Russian legislative and regulatory framework is made. Recommendations are given to improve the methodology and practice of abandonment funds management in Russia.

Effects of gamma radiation treatment on three different medicinal plants: Microbial limit test, total phenolic content, in vitro cytotoxicity effect and antioxidant assay.

BACKGROUND AND AIM: The aim of this study is to evaluate the effects of gamma radiation treatment on three medicinal plants, namely Euodia malayana, Gnetum gnemon and Khaya senegalensis at two different forms; methanol leaf extracts and dried leaves respectively. EXPERIMENTAL PROCEDURE: The microbial limit test (MLT) studies indicated the suitable dosage of minimum and maximum gamma irradiation for leaf extracts as well as dried leaves of all the tested medicinal plants. Quantitative analysis of total phenolic content (TPC) analysis is based on calorimetric measurements determined using the Folin-Ciocalteu reagent with gallic acid (GA) used as the reference. In vitro cytotoxicity assay by using fibroblast (L929) cell lines was performed on each plant to determine the toxicity effect which sodium dodecyl sulfate (SDS) as the positive control. DPPH (2,2-diphenyl-1-picryl-hydrazyl) assay was conducted by using vitamin C and GA as the positive controls to determine the antioxidant property of each plant. RESULTS AND CONCLUSION: The MLT analysis indicated that the suitable dosage gamma irradiation for leaf extracts was 6-12 kGy and dried leaves were 9-13 kGy. The amount of GA concentration in each plant increased significantly from 30-51 mg GAE g-1 before treatment to 57-103 mg GAE g-1 after treatment with gamma radiation. This showed no significant effect of in vitro cytotoxicity activity before and after treatment with gamma irradiation in this study. Effective concentration (EC50) values of Khaya senegalensis plant reduced significantly (P ≤ 0.005) from 44.510 µg/ml before treatment to 24.691 µg/ml after treatment with gamma radiation, which indicate an increase of free radical scavenging activity.

Determination of N-Nitroso-N-Methyl-4-Aminobutyric Acid in Losartan Potassium Using High Performance Liquid Chromatography Triple Quadrupole Mass Spectrometry / 中国药学杂志

OBJECTIVE: To establish a method to determine the genotoxic impurity, N-nitroso-N-methyl-4-aminobytyric acid, in losartan potassium using high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-MS/MS). METHODS: The method was developed by using Shimadzu Shim-pack XR-ODS II column (2.0 mm×150 mm, 2.2 μm). Time program was conducted with mobile phase consisting of water (0.1% formic acid, A) and methanol (B). The flow rate was 0.3 mL•min-1, and the column oven temperature was maintained at 40 ℃. The samples were ionized by electrospray ionization (ESI) with multi reaction monitoring (MRM) data acquisition mode. The collision energies were -11, -13, and -13 V, CID gas was argon with pressure of 270 kPa.3 pairs of precursor, and product ions (m/z) of NMBA were 147.15→117.10, 147.15→87.10, and 147.15→44.10, respectively. RESULTS: The genotoxic impurity NMBA showed linearity between 1 and 100 ng•mL-1 with correlation coefficient of 0.999 9. The intra-day and inter-day repeatability was examined by relative standard deviations (RSDs) of retention time and peak area (RSD<1.10%, n=6 for intra-day repeatability and n=18 for inter-day repeatability). The accuracy was examined by percent recovery at three concentration levels, and the average percent recovery was between 94.40% and 98.04%. CONCLUSION: The established LC-MS/MS method is efficient for limit test and quantitation of NMBA in losartan potassium bulk drug.

Limit Test of Camphor in Niuhuang Qingxin Pills (Prescription of the Bureau) / 医药导报

Objective To establish limit test method of camphor in Niuhuang qingxin pills (prescription of the bureau) . Methods The separation was performed on an HP-INNOWAX capillary column (0.25 mm×30 m, 0.25 μm) and the column temperature was 110 ℃ . The temperatures of the inlet and the FID detector were 200 and 230 ℃ , respectively. The flow rate of the carrier gas was 1.8 mL·min-1 and the split ratio was 10:1. The injection volume was 1 μL. Results Good linearity was obtained for camphor within the range of 1.65 to 165 μg·mL-1, and the average recovery of low, medium, high concentration were 99.12％, 99.56％ and 99.56％, respectively,with RSD were 1.01％,0.69％ and 0.38％, respectively. Trace camphor was found in 7 samples out of 38 samples from 9 manufactures. Conclusion The proposed method was accurate, sensitive and simple, and was suitable for quality evaluation and safety control of Niuhuang qingxin pills (prescription of the bureau) .

Bending Limit Tests for Ultra-Thin Liquid Crystal Polymer Substrate Based on Flexible Microwave Components.

In this paper, bending limit tests for one ultra-thin liquid crystal polymer (LCP) substrate (Rogers 3850) based on the mechanical properties of flexible microwave microstrip components are presented. First, a set of 50 Ω microstrip lines, a band-pass filter, and a stepped impedance filter in X-band, are designed by using double clapped LCPs with 50 µm thickness of substrate and 18 µm thickness of copper, which is fabricated by conventional photolithography. Then, the limit tests of the flexibility of the LCP microwave microstrip components are presented, and the range of the bending limit radius, from 1 mm to 0.75 mm, is demonstrated from the testing results. It is found that the cause for component failure is fracture of the copper (18 µm thickness) laminate, according to the bending limit test experiments. Finally, the analysis of the reasons for the collapse of the microwave components, under bending situations, is explored. The results from this work would be useful for further designs of the flexible microwave devices and systems on LCP substrates, with compact sizes and good performance.

Improvement of the Quality Standard for Fuzheng Capsules / 中国药师

Objective: To establish the quality standard for Fuzheng capsules. Methods: TLC was adopted to identify Astragali Radix and Glycyrrhiza uralensis. The method validation for Fuzheng capsules was conducted by microbial limit test as described in the appendixes of Chinese Pharmacopeia (2015 edition). The content of epimedii in Epimedium brevicornu was determined by HPLC. The chromatographic separation was carried out on an Agilent TC-C18(2) (250 mm×4. 6 mm, 5 μm) column. The mobile phase consis-ted of acetonitrile-water( 30: 70) with gradient elution at a flow rate of 1. 0 ml·min-1,and the injection volume was 5 μl. The detec-tion wavelength was 270 nm. Results: The spots in TLC were clear without any interference. The methods of plating and direct inocu-lation could be used for the microbial limit test. The linear range was 0.101-1.008 μg (r =0.999 7). The average recovery was 99. 36% with the RSD of 0. 81% (n=6). Conclusion: The method is simple with high specificity and good repeatability, which can be used as the quality control method for Fuzheng capsules.

Analysis of Microbial Contamination Status of 9 Kinds of Chinese Herbal Pieces from Guangxi Regions / 中国药师

Objective:To investigate the microbial contamination status of Chinese herbal pieces from Guangxi regions and provide reference for the microbial limit standard. Methods:According to Chinese Pharmacopoeia (2015 edition), the herbal pieces were analyzed for the total number of aerobe microbial, yeasts, molds, thermophilic bacteria and bile-resistant gram-negative bacteria,and salmonella was also detected. Results:In 90 batches of Chinese herbal pieces,the lg average value of the total number of aerobe microbial was 3.7,and that of the total yeasts and molds was 1.7,that of thermophilic bacteria was 0.9 and that of bile-resistant gram-negative bacteria was 1.1,and Salmonella was not detected out. There were statistically significant differences (P < 0.05) in the microbial contamination levels of herbal pieces with different processing techniques and packaging materials. Conclusion:According to different processing methods and administration, microbial limit standard should be established for classification in order to guide the standardized production of Chinese herbal pieces and improve their quality gradually.

Interference Elimination of Matrix Magnesium Sulfate on the Microbial Limit Test for Urea Cream / 中国药师

Objective:To eliminate the interference of matrix in urea cream on the microbial limit test. Methods: A certain a-mount of magnesium sulfate was added to the test solution followed by stirring and placing sometime to make the cream layering, and the water layer was used for the microbial limit detection. Results:After magnesium sulfate was added to urea cream, microbial limit test was not affected by the matrix. The average recovery of Escherichia oli, Staphylococcus aureus, Bacillus subtilis, Candida albicans and Aspergillus niger was 96. 00%, 97. 00%, 100. 00%, 99. 00% and 101. 00%, respectively. The negative and positive results of Psudomonas aeruginosa and Staphylococcus auress were reliable. Conclusion:In the detection of microbial limit for urea cream, mag-nesium sulfate can be used as a good auxiliary agent to make the detection method more convenient and reliable.

Study on Microbial Limit Test Methods for Three Preparations Containing Chlorhexidine Acetate / 中国药师

Objective:To establish the microbial limit test methods for three preparations containing chlorhexidine acetate. Meth-ods:The validation of microbiological limit test for three preparations including chlorhexidine acetate solution, chlorhexidine acetate ointment and chlorhexidine acetate cream was carried out respectively using the conventional method,dilution method,membrane filtra-tion method and neutralization method. Results:The recovery rates of five strains in the verification of counting method by membirane filtration and nearailzation method were more than 50%. Every positive test micrcorganism could be detected while negative control bacteria could not grow in the examination of control bacteria.Conclusion:The membrane filtration method can be used for the deter-mination of control bacteria for chlorhexidine acetate solution and chlorhexidine acetate ointment,and the neutralization method can be applied in the determination of control bacteria for chlorhexidine acetate cream.

Study on the Method of Microbial Limit Test for Preparation Liquid of Iron Sucrose Injection before Filtration and Sterilization / 中国药房

OBJECTIVE:To establish a method of microbial limit test for liquid preparation of Iron sucrose injection before filtration and sterilization.METHODS:According to the microbial limit test in the 1005 and general rules 1006 of 2015 edition of Chinese Pharmacopoeia (vol.Ⅴ),plate method and membrane filtration method were used to measure total number of aerobic bacteria (Staphylococcus aureus,Pseudomonas aeruginosa,Bacillus subtilis,Candida albicans,Aspergillus niger) and total number of molds and yeasts (C.albicans,A.niger).The optimal test method was obtained by comparing the bacterial recoveries.RESULTS:By plate method,the recoveries of P aeruginosa and B.subtilis were 2％ and 5％.The test sample was diluted 10 times with pH 7.0 sodium chloride-peptone buffer solution,and the bacterial recoveries were in the range of 88％ to 96％;but he medium was dark in color.By membrane filtration method,without rinse solution,the bacterial recoveries in the range of 88％ to 95％.Add rinse solution,the bacterial recoveries were in the range of 91％ to 103％.After validated,the recoveries of menbrane filtration method with tlushing fluid ranged 50％-200 ％,which was in line with the requnements.CONCLUSIONS:The membrane filtration method established in this experiment has higher bacterial recovery rate than the plate method.The bacterial recoveries rate were higher after adding rinse solution,and no dark substance in the surface of filter membrane affect the accotmt.It can be used as the microbial limit test method for preparation liquid of Iron sucrose injection before filtration and sterilization.

Validation of Microbial Limit Test for Compound Benzocaine Gel / 中国药师

Objective: To establish a microbial limit test method for compound benzocaine gel.Methods: According to the general principles of Chinese Pharmacopoeia (2015 edition), method applicable experiments were performed respectively for the routine method, neutralization method and dilution & neutralization method.Using the recovery ratio of test bacteria as the index, the medium of dilution & neutralization method was adopted in the total aerobic microbial count and total combined yeasts and molds count, and the neutralization method was used for the control bacteria detection.The neutralizing agents were polysorbate 80 and lecithin.Results: The method of dilution & neutralization could eliminate the bacteriostasis of the drug, and the recovery ratio of each test bacteria was within the range of 0.5-2.0, which was in line with the requirements of Chinese Pharmacopoeia.Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus could be detected out in the positive control bacterial test,and bacteria were not detected out in the negative test.Conclusion: The method can be used for the microbial limit test for compound benzocaine gel.

Neutralization of Lecithin and Polysorbate-80 in Antibacterial Activity of Traditional Chinese Medicine Preparations / 中国药师

Objective:To investigate the neutralization of lecithin and polysorbate-80 in antibacterial activity of oral solid tradition-al Chinese medicine preparations without Chinese medicinal herb powder. Methods:According to the requirements in Chinese Pharma-copeia (2015 edition), the applicability of microbial counting method was tested in the diluent containing lecithin and polysorbate-80 and the conventional diluent, respectively, and the results were compared. Results: The recovery results of applicability of microbial counting method using neutralizers (lecithin and polysorbate-80) conformed to the standard of Chinese pharmacopoeia (2015 edition). Conclusion:The combination of lecithin and polysorbate-80 has notable neutralization in antibacterial activity of oral solid traditional Chinese medicine preparations without Chinese medicinal herb powder.

Methodological study on microbial limit test of zinc oxide and talcum powder lotion / 药物评价研究

Objective To establish a method for the microbial limit test of zinc oxide and talcum powder lotion in Chinese Pharmacopoeia 2015.Methods Microbial enumeration test and specified microorganisms test with instructions were conducted from Chinese Pharmacopoeia 2015,which involved 10 batches zinc oxide and talcum powder lotion and five species of bacteria in all.The samples were treated by centrifugation and membrane filtration.Microbial enumeration test:the total number of aerobic bacteria using TSA medium to examine,strains were Staphylococcus aureus,Pseudomonas aeruginosa,Bacillus subtilis,Candida albicans,and Aspergillus niger;The total number of molds and yeasts using SDA culture medium to examine,strains were Candida albicans and Aspergillus niger.Each strain was divided into two groups:Adding bacteria test group and bacteria control group.Samplecontrol group and negative control group of each culture medium was prepared respectively.Count the colonies and calculate the rate of recovery.Specified microorganisms test:Pseudomonas aeruginosa and Staphylococcus aureus were applicated and set the bacteria validation group,sample control group,and negative control group.The culture medium of each group was crossed on the corresponding medium plate,and Microflex LT mass spectrometer was used to identify the bacteria.Results The recoveries of all kinds of strains in microbial enumeration test,total yeast and mold count were 0.75-1.16 in all batches.In the validations of Staphylococcus aureus and Pseudomonas aeruginosa,all kinds of strains were respectively detected in bacteria validation group,and there were no bacterial growth in sample control group and negative control group.Conclusion The microbiological examination methods for zinc oxide and talcum powder lotion can meet the requirements of Chinese Pharmacopoeia 2015.

Verification of Microbial Limit Test Methods for Three Kinds of Preparations with Heavy Metals / 中国中医药信息杂志

Objective To establish the methods of microbial limit test for three kinds of preparations with heavy metals, such asDingxian Pills,Pizhi Lotion andJiawei Huangqin Ointment.Methods According to Chinese Pharmacopoeia 2010, the recovery rates of bacteria, fungus and yeast treated by three preparations were detected. And the methods of testing control bacteria were also validated.Results Culture medium dilution method was proved to be applicable forDingxian Pills. Culture medium dilution method combined with pre-filtration method was proper for Pizhi Lotion. And the extraction method was adopted forJiawei Huangqin Ointment. The recovery rates of these five validation strains reached 70% by appropriate methods. And the same methods were used for validation of the control bacteria.Conclusion The methods of microbial limit test for these three different preparations were established through this study.

Establishment of Microbial Limit Test of Jingzhi Guanxin Tablets / 中国药师

Objective:To establish a method for the microbial limit test of Jingzhi Guanxin tablets. Methods: According to the methods in the 2010 edition and 2015 edition of Chinese Pharmacopoeia, the test was performed respectively. Results:Jingzhi Guanxin tablets showed obvious inhibitory effect on Bacillus subtilis. The bacteria count could be carried out by the culture medium diluting methods in the 2010 edition. The total amount of aerobe could be detected by the membrane filtration method in the 2015 edition. The total combined molds and yeasts count could be performed by the plate count method and the specified microorganism could be tested with the routine method. Conclusion:The above methods can be used for the microbial limit test of Jingzhi Guanxin tablets.

Validation of microbial limit tests for compound Hongjingtian oral liquid / 药学实践杂志

Objective To establish a method of microbial limit tests for compound Hongjingtian oral liquid and to per-form the validation of the method.Methods The validation on the microbial limit test method was conducted according to the counting method of bacteria,mycetes and yeasts and the control bacteria test method stated in the appendix of China pharmaco-poeia (2010 edition).Results The recoveries were over 70% when culture diluting method was used for staphylococcus aureus and routine test method was used for Escherichiacoli,Bacillus subtilis,Candida albicans and Aspergillus niger.In the test of positive control bacteria,the growth was detected,while the negative control was no growth detected.Conclusion The micro-bial limit test for compound Hongjingtian oral liquid is validated in this study.The amount of staphylococcus aureus can be de-termined using diluted culture method ;while the amounts of Escherichiacoli,Bacillus subtilis,Candida albicans,Aspergillus niger can be determined by conventional method.

A Validated HPLC/MS Limit Test Method for a Potential Genotoxic Impurity in Cilostazol and its Quantification in the API and in the Commercially Available Drug Product.

Cilostazol is a selective inhibitor of type 3 phosphodiesterase. 5-(3-Chloropropyl)-1-cyclohexyl-1H-tetrazole, used as an intermediate in the synthesis of cilostazol, has a primary alkyl chloride group, a well-known alerting function for genotoxic activity. Upon request from a regulatory agency, a limit test in accordance with ICH Q2(R1) added with the accuracy of a recovery test of 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole in cilostazol was developed and validated. The application of the method highlighted the need to optimize the purification process to ensure levels of this potential genotoxic impurity in the final active pharmaceutical ingredient below the established limit. Also, the analytical method was suitable to determine the amount of the impurity in samples of the commercially available drug product, which showed the levels to be above the established threshold of toxicological concern (TTC).