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Ezetimibe, a lipid-lowering drugs, is classified as selective cholesterol absorption inhibitor by blocking cholesterol absorption from the small intestine. Ezetimibe can be used alone or in combination with other hypolipidemic drugs for control the blood cholesterol levels. In the fiscal year 2018, Bureau of Drug and Narcotic held Quality Assurance of Medicine Program to survey the quality of Ezetimibe tablets. All samples were randomly sampling from public hospitals nationwide. Samples from importers were also collected by cooperating with Thai Food and Drug Administration. A total of 18 samples were obtained in strength of 10 milligrams from 2 foreign manufacturers (3 registration numbers). The samples were evaluated according to the United States Pharmacopeia (USP 40) for identification, assay, content uniformity, organic impurities and dissolution. The analytical method was verified prior to sample testing. The results showed that all samples complied with pharmacopeia specification. It can be concluded that the quality of Ezetimibe tablets in Thailand has satisfactory pharmaceutical characteristics. Keywords: Ezetimibe / Quality Assurance of Medicine Program

Lamivudine and zidovudine belong to the class of nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs, which are in the National List of Essential Medicines for the treatment of HIV infection. However, their qualities have not yet been surveyed. Thus, for the fiscal year 2018, Bureau of Drug and Narcotic conducted a drug quality assurance program on the fixed-dose combination products of lamivudine and zidovudine. A total of 10 samples from one local manufacturer and one importer were evaluated using a verified method according to USP 40. Tests for identification, assay, weight variation, content uniformity, organic impurities and dissolution were performed. The results showed that all products complied with every requirement. It can be concluded that quality of the lamivudine and zidovudine tablets was optimal. Keyword : lamivudine and zidovudine tablets, quality

Lamivudine belongs to the class of nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs for the treatment of HIV and hepatitis B infection. Lamivudine was included in the antiretroviral regimen recommended by WHO Guideline 2003; however, its quality has not yet been surveyed. In the fiscal year 2018, pharmaceutical quality of the lamivudine tablets were evaluated by the Bureau of Drug and Narcotic. Twenty-three samples were randomly collected from the public hospitals and the manufacturers. The samples consisted of three strengths of 100, 150 and 300 mg tablet with 5 registration numbers. They were produced from one local manufacturer and imported from two companies. The verified analytical methods as per the USP 40 including identification, assay, weight variation, organic impurities and dissolution were performed. The results showed that all tested samples met the acceptance criteria. Thus, it indicated that lamivudine tablets prescribed in Thailand possessed the satisfactory pharmaceutical characteristics. Keywords: Lamivudine tablets, quality

Bureau of drug and narcotic, Department of Medical Science is the main unit which is responsible for the analysis of microbial contamination in traditional medicine for registration. According to the announcement of Thai FDA regarding the microbiological test of traditional medicine for registration, Staphylococcus aureus/gram, Salmonella spp. /10 grams and Clostridium spp. /10 grams should be absent. The test method used follows the TP Supplement 2005. The microbial count in the 828 samples of the traditional medicine registered at Thai FDA during 2014-2018 was investigated. In 2014, 20 samples from 203 samples (9.85%) failed. In 2015, 39 samples from 235 samples (16.59%) failed. In 2016, 34 samples from 158 samples (21.5%) failed. In 2017, 9 samples from 118 samples (7.62%) failed. In 2018, 17 samples from 114 samples (18.5%) failed. The microbial found in the sample was Clostridium spp. Generally, Clostridium spp. is found in soil and can be diarrhea disease. This indicates that the manufacturing process and quality control of the products need improvement by use raw data of research for manufacture guideline. Keyword: Clostridium spp.

Aminophylline is listed in class A of the National List of Essential Medicines 2018. Aminophylline is a Xanthine derivative which is utilized as bronchodilator. In the fiscal year 2018, aminophylline injections were chosen to study for the quality. A total of 11 samples were collected from public hospitals and manufacturer (2 registration numbers). The samples were evaluated according to the United States Pharmacopoeia specification (USP 40) for assay, pH, content of Ethylenediamine, organic impurities, particulate matter, sterility and bacterial endotoxins.The result showed that 5 samples were complied with the pharmacopoeial specifications. Meanwhile, 6 fail to meet the requirement in content of Ethylenediamine and pH (4 samples for content of Ethylenediamine and pH and 2 samples for content of Ethylenediamine). The information obtained will be useful for supporting the drug procurement in hospitals. Key words : Aminophylline, Ethylenediamine

Drug testing in urine is a screening test used to identify a drug addict who is considered as a patient with treatment requirement. Test results with accuracy and precision are, therefore, essential. Our aim was to develop laboratory capacities on analysis of narcotics in urine specimens using 4 activities that were establishing proficiency testing (PT) programs for screening and confirmatory tests, providing training courses, empowering visit to participating laboratories and publishing guidelines for urine drug testing. PT panels for both programs were consisted of methamphetamine, morphine and marijuana that are the majority of drugs used in Thailand. The participating laboratories in the PT programs were shown to be increasing from 627 to 689 laboratories during October 2013 to September 2016. Laboratory performance in both PT programs was analyzed for developing a training curriculum and planning for empowerment during on-site visits, leading to continuous quality improvement of PT provider and its participants. In addition, two published guidelines on urine drug testing were resulted from a 3-year operation of PT programs. Taken together, all activities performed were useful for enhancing potential of narcotics testing laboratories in Thailand. http://dmsc2.dmsc.moph.go.th/net/BDMS/data/6028596.pdf

Substandard medicines have a great impact on health systems. For example, they can engender drug resistance, adverse effects, drug toxicity, increase mortality and morbidity, etc. As a result, a larger budget is needed for longer healthcare treatment, while health personnel lose confidence in drug quality monitoring and generic drugs. This study employs a descriptive retrospective design. It aims to analyze the database of test results from the Quality Assurance of Medicines Program, which was operated by the Department of Medical Sciences between the fiscal years of 2002 to 2016. The international pharmacopoeia, for example, the United States Pharmacopeia (USP) or British Pharmacopoeia (BP), were used as reference standards. The findings revealed that 428 government hospitals voluntarily sent medicine samples to the Quality Assurance of Medicines Program. The total number of modern medicine samples was 572 items or 16,212 samples. The number of substandard samples decreased from 19.0% in 2002 to 0.8% in 2016. Based on the latest 3-year data, 2.9% of domestic generic drugs failed the standard specifications, whilst 0.9% of imported drugs failed. Dissolution and content of active ingredients were the most common issues found. The corresponding organizations in pharmacovigilance and pharmaceutical manufacturing, for example, the Thai Food and Drug Administration (Thai FDA), the Department of Medical Sciences (DMSc), the Government Pharmaceutical Organization (GPO), and the Thai Pharmaceutical Manufacturers Association (TPMA) should cooperate to monitor and improve the quality of domestic generic drugs in order to achieve greater confidence in using domestic generic drugs while also making budget savings. This could also strengthen the domestic pharmaceutical industry and enhance national drug security. http://kb.hsri.or.th/dspace/handle/11228/4861

Even though direct contact technique was used to screen the cytotoxicity of plastic parenteral containers according to TIS 531, some difficulties were encountered when samples having bag and bottle forms were found moving in the wells during testing. In order to be able to test all types of containers, agar diffusion technique was applied to evaluate 34 plastic parenteral containers parallel with direct contact technique. The L-929 cultures were grown to monolayer in Eagle’s Minimum Essential Medium (MEM) supplemented with 5% fetal bovine serum (FBS). After incubation, the agar layer (1.5%) supplemented with MEM in 5% FBS and neutral-red stain was added to replace the medium. The samples were cut and placed on the agar layer. After 24–hour exposure, the cell monolayers were observed for cell deaths beneath and surrounding the samples as well as changes in morphology and cell densities. In this study, USP Positive Bioreaction RS were used as positive material control. There were no statistical differences between both techniques (P>0.05). However, the agar diffusion technique was a useful method for screening plastic parenteral containers made from polyethylene, polypropylene, polyvinyl chloride and laminar. Therefore, it could be another useful method to be implemented for the cytotoxicity testing scheme in order to replace the direct contact technique. http://budgetitc.dmsc.moph.go.th/research/pdf/20159.pdf

Analytical results of amphetamines in urine are significant evidence of the legal proceedings. The methods used in the analysis must be highly effective. Bureau of Drug and Narcotic developed two fast, accurate and precise gas chromatography–mass spectrophotometry (GC-MS) and liquid chromatography - mass spectrophotometry (LC-MS) methods for qualitative and quantitative determination of amphetamines in urine. Amphetamines were extracted from urine by solid phase extraction method. The proposed method proved to be specific and selective without interference from urine matrixes. For GC-MS method, the linearity and range were 100-4,000 nanograms per milliliter for amphetamine and methamphetamine with correlation coefficients greater than 0.99. Mean percentage recoveries for amphetamine and methamphetamine were 75.40 and 76.89, respectively. Inter-day accuracy for all drugs range from 0.34 to 17.23 % RD. Inter-day precision for all drugs range from 3.84 to 12.57 % CV. The uncertainties at a confidence level of 95 were 2.00 ± 0.39 micrograms per milliliter and 2.00 ± 0.35 micrograms per milliliter, respectively. For LC-MS techniques, the linearity and range were 300-2,000 nanograms per milliliter for amphetamine and methamphetamine with correlation coefficients greater than 0.99. Inter-day accuracy for all drugs range from 2.22 to 16.11 % RD. Inter-day precision for all drugs range from 2.36 to 10.43 % CV. The uncertainties at a confidence level of 95 were 2.00 ± 0.27 micrograms per milliliter and 2.00 ± 0.24 micrograms per milliliter, respectively. The unit cost of material cost for the analysis by GC-MS and LC-MS are 628 baht and 438 baht, respectively. Therefore, the developed methods are applicable for analysis of amphetamines in urine with in the assigned level of narcotic acts. https://he02.tci-thaijo.org/index.php/dmsc/article/view/241912/164637

The quantitative determination of the adulterated dexamethasone and prednisolone in traditional drug was developed by using high performance liquid chromatography (HPLC) with reversed phase C8 column (Hypersil BDS) and a mixture of acetonitrile and purified water as a mobile phase. The sample solution was cleaned up by solid phase extraction (SPE). The method validation data showed good linearity at the concentration range of 250-12,500 μg/L with the correlation coefficient of 0.9987 and 0.9988 for dexamethasone and prednisolone, respectively. Accuracy and precision were performed by adding 500, 6,000 and 12,000 μg/L of each of dexamethasone and prednisolone to sample matrix. The percentages of recovery were 100.30-104.53 and 100.02-102.18 for dexamethasone and prednisolone, respectively. The relative standard deviations of dexamethasone and prednisolone were 0.04-2.01 and 0.15-2.47, respectively. The limit of quantitation of dexamethasone and prednisolone are 250.14 and 249.30 μg/L, respectively. Therefore, the developed HPLC method is suitable for surveillance of the dexamethasone and prednisolone adulterants in traditional herbal medicines. https://he02.tci-thaijo.org/index.php/dmsc/article/view/242649

The development and validation of reversed phase high performance liquid chromatography (RP-HPLC) method for the determination of azithromycin capsules and azithromycin for oral suspension was established. The separation was achieved on a XTerra C18, 5-μm, 4.6 × 150 mm column, at 50 degree Celsius. The mobile phase was the mixture of acetronitrile, methanol and dibasic potassium phosphate with sodium 1-octanesulfonate pH 8.20 (21:40:39, v/v) at the flow rate of 1.5 ml per minute, setting the detection at 210 nm. Specificity test indicated that azithromycin peak was not interfered by its degradation product peaks from any stress conditions : heat, light, acid/base hydrolysis and oxidation. The described method was linear over the range of 0.1-0.6 mg per ml for azithromycin with correlation coefficient, r, 0.9979. The percentage mean recovery of azithromycin capsules and azithromycin for oral suspension were 99.48 (%RSD = 0.28) and 99.20 (%RSD = 0.61), respectively. The repeatability of azithromycin capsules and azithromycin for oral suspension were performed with %RSD 1.3 and 1.1, respectively. The intermediate precision data (%RSD) obtained among different days, analysts and HPLC instruments of azithromycin capsules and azithromycin for oral suspension were 1.4 and 1.1 respectively. The results showed that this method was robust when HPLC conditions such as the HPLC column, the pH of buffer solution, the ratio of mobile phase, the column temperature and even the flow rate, were changed. The proposed analytical method presented here revealed that it was suitable for the determination of azithromycin capsules and azithromycin for oral suspension. This validated method was further used to analyze azithromycin capsules and azithromycin for oral suspension; it was found that all of the samples complied with the specifications. https://he02.tci-thaijo.org/index.php/dmsc/article/view/241957

Graphite Furnace Atomic Absorption Spectrophotometry (GFAAS) method was developed and validated for the determination of arsenic (As), lead (Pb) and cadmium (Cd) in herbal medicines. Samples were prepared by wet digestion. Validation was performed according to the International Committee on Harmonization (ICH) Guidelines. The proposed method permitted the determination of As, Pb and Cd in the ranges of 5-80 ng/ml, 10-80 ng/ml and 0.25-4.0 ng/ml, respectively, with correlation coefficients greater than 0.999. Limit of detection (LOD) were found to be 2.5 ng/ml, 2.5 ng/ml and 0.16 ng/ml for As, Pb and Cd, respectively, while limit of quantitation (LOQ) were found to be 1 μg/g, 2 μg/g and 0.1 μg/g for As, Pb and Cd, respectively. Mean percentage recoveries were in the range of 98.8-105.6 while intra- and inter-day precisions were less than 4.7% for all three heavy metals. The method was successfully applied to the study of heavy metal contamination in herbal medicines available in Thailand. A total of 86 samples were investigated and the results showed that all test samples contained As, Pb and Cd lower than the limit specified in the Thai Herbal Pharmacopoeia. https://he02.tci-thaijo.org/index.php/dmsc/article/view/241959

The method transfer and validation for the determination of Prednisolone in tablets was established using Ultra Performance Liquid Chromatography (UPLC). The separation was achieved on a ZORBAX Eclipse Plus C18 (1.8 μm, 2.1 × 100 mm) at 35 degree Celsius. The mobile phase was the mixture of methanol and water (55:45, v/v) at the flow rate of 0.3 ml per minute with UV detection at 254 nm. Specificity test showed that prednisolone peak was not interfered by its degradation product peaks under stress conditions: acid, base, heat, hydrolysis, oxidation and light. The linearity test showed linear relationship between the area under the peak and the concentration levels in the range of 0.15-0.25 mg per ml with correlation coefficient, r, 0.9999. The percentage mean recovery from three concentration levels was 100.5 (% RSD = 1.17%). The precision test was performed by the assay of six samples within the same day, and different days and analysts gave % RSD of 0.7, 0.6 and 0.7, respectively. The robustness test indicated that the described method was robust when the chromatographic conditions were changed such as column batch, column temperature, composition and flow rate of mobile phase with no effect on the system suitability and the test result. This method takes less analytical time than the method specified in the United States Pharmacopoeia and British Pharmacopoeia. Therefore, the proposed method was suitable for the quantification of prednisolone in tablets and could be used as an alternative method. https://he02.tci-thaijo.org/index.php/dmsc/article/view/242344

Rationale and Objective: Reflux extraction is the standard sample preparation method described in the Thai Herbal Pharmacopoeia (THP) for the assay of andrographolide content in both Andrographis herbal material and capsules, and has been used since 1995. The disadvantages of this method are the consumption of large amounts of volatile and hazardous organic solvents, low extraction efficiency and a time-consuming process. The objectives of this study were to compare the extraction efficiency of ultrasonication and reflux extraction methods and to propose an alternative to the current THP method for quality control of Andrographis capsules. Methodology: Optimization of extracting solvent and sonication time were investigated. The best condition was further used for comparison of the extraction efficiency with reflux extraction. A total of 30 different lots of Andrographis capsules were tested. The analytical method as described in the THP was revalidated to ensure method performance and data integrity after the sample preparation had been changed. Results: Ultrasonication with 50% methanol for 15 minutes gave the highest andrographolide content extracted. Changes in sample preparation did not affect the analytical method performance. The contents of andrographolide extracted using ultrasonication were comparable and in most cases they were even higher than those obtained from the reflux method. Discussion and Conclusion: Ultrasonication is a more efficient, rapid and convenient method and can be used as an alternative sample preparation method to the current monographs in THP for the quality control of both Andrographis herbal material as well as medicinal products. https://he01.tci-thaijo.org/index.php/JTTAM/article/view/115106

DNA Fingerprinting in Herbal Medicine for Thai Herbal Pharmacopoiea.

Amoxicillin and Clavulanic acid combination is the well-known dosage form of antibiotics. It was developed to improve the efficiency and optimize the effects. The crucial problem of this dosage form is its stability due to the tendency to degrade. To assure the quality of the products, the amoxicillin and clavulanic acid tablets have been chosen to study under the project “Quality Assurance of Medicines under the Universal Health Care Coverage” by Bureau of Drug and Narcotic, Department of Medical Sciences. The pharmaceutical testing was performed and evaluated using the verified method and in compliance with the USP 34 monograph. The total number of samples was 131. The samples came from 42 drug dossiers which were from four Thai local manufacturers and fifteen international ones. The samples were tested on the following topics: assay, weight variation, content uniformity, dissolution, and water determination. The results showed that 122 samples (93%) passed and 9 samples (7%) failed to meet the quality standards. The failed samples were one for the assay of clavulanic acid, two for the content uniformity of clavulanic acid, one for both the assay and content uniformity of clavulanic acid, and five for dissolution testing. The study revealed that the quality problems of Amoxicillin and Clavulanic acid Tablets still exist. Hence, the manufacturing process, the quality of ingredients, as well as the packaging and storage procedures play the important role in the quality of products. https://he02.tci-thaijo.org/index.php/dmsc/article/view/241702

Vaccines in Thai Pharmacopoeia

The wide spread of amphetamine abuse has caused serious problems to Thailand. The content analysis is one approach to control and suppressing the spread of amphetamine tablets. In order to determine the composition of amphetamine tablets, between October 2006 to September 2013, the situation on amphetamine tablet composition was evaluated. The authors collected database from Bureau of Drug and Narcotic, Department of Medical Sciences, for the qualitative and quantitative data of 44,140 samples of amphetamine tablets sent from the authority under the Royal Thai Police Headquarters. By using thin layer chromatography and gas chromatographic technique, the results showed that, for qualitative information, most amphetamine tablets consisted of methamphetamine hydrochloride and caffeine. The percentage by weight of methamphetamine hydrochloride quantitative detection was in the range of 0.00 to 40.00. From the seven years data, the highest range of percentage for methamphetamine hydrochloride detection was 15.01 to 20.00 from 32.98 to 83.86 percent of the total samples. There were also other ingradients in the drugs, such as N,N-dimethylamphetamine, ephedrine, paracetamol, chlorpheniramine maleate and diphenhydramine. Therefore, this study revealed the high incidence of amphetamine use, both the composition and the distribution. Therefore, information from this study is useful for the development of effective prevention programs to control illicit drugs in the country. http://thaidj.org/index.php/JHS/article/view/282

The bacterial endotoxins test was used to measure the levels of bacterial endotoxin contamination in 248 samples from 16 parenteral injections under the Drug Quality Assurance Program. The interference test and kinetic turbidimetric method for the determination of endotoxin in each sample were performed simultaneously. The concentration used in this study did not inhibit or enhance with the detection of endotoxin with Limulus test. The resulting data is a useful information for manufacturers in setting up a suitable concentration for bacterial endotoxins testing. Furthermore, the results showed that all samples contained endotoxin level less than endotoxin limit. The quality and safety of parenteral drugs used in public hospitals all over the country met the requirement of bacterial endotoxin test.