Document

According to The Narcotics Control Act of 2519 B.E., anybody who is detected morphine in urine at the 300 ng/ml cutoff threshold, they will be reported as the drugs user. However, opium, codeine, heroin, or morphine user can meet morphine in urine. However, 6MAM can use to identify using morphine and Codeine-morphine ratio above 1 use to identify using codeine. Thus, these sunstances can derive the sources of morphine. The aim of the present work was to derive the sources of morphine in body fluids and quantification of morphine correctly using on-line solid phase extraction-liquid chromatography-tandem mass spectrometry. morphine-d3 and 6MAM-d3 are used as internal standard. Extraction by online SPE. Separation was performed on an ion-exchange column and detected by tandem mass spectrometry with electron spray ionization, positive mode. The method was validated according to the FDA guidance. Limit of 6MAM detection is 1 ng /ml. The linear range of codeine and morphine were obtained from 100-2000 ng/mL. This developed method was successfully using for quantification of morphine in human urine and its source. Can apply the method for classification of drug user in routine job of department of medical science Keywords : Morphine, Codeine, Heroine, 6MAM, urine

Diclofenac Sodium tablet is a nonsteroidal anti-inflammatory drug (NSAID). It is used to treat mild to moderate pain, inflammatory of osteoarthritis, rheumatoid arthritis and acute gout attack. In the fiscal year 2019, Bureau of Drug and Narcotic collaborated with Food and Drug Administration Thailand randomly collected samples from manufacturers, importers and hospitals under Quality Assurance of Medicine program. A total of 23 samples with strength of 25 and 50 mg from one importer (1 registration number) and 8 local manufacturers (9 registration numbers) were evaluated according to the United States Pharmacopoeia (USP 41) for identification, assay, content of uniformity, dissolution and organic impurities. The analytical methods were verified prior to analysis. The survey showed that 21 samples (91 percentage) complied with the USP 41 specifications whereas only 2 samples failed in dissolution. These data will be published in the GREEN BOOK. Key words : Diclofenac Tablet, Diclofenac sodium, NSAID

Atorvastatin Calcium is an antilipidemic drug which is listed in Thai National List of Essential Medicines. In the fiscal year 2019, the Bureau of Drug and Narcotic performed the quality assurance of Atorvastatin Calcium Tablets in accordance with the United States Pharmacopeia (USP 41). The method was verified prior to sample testing. A total of 55 samples with strengths of 10, 20, 40 and 80 mg were collected from public hospitals and manufacturers which consisted of 1 registration number from 1 local manufacturer and 11 registration numbers from 2 overseas manufacturers. All samples presented satisfactory results which complied with pharmacopeial specifications by performing assay, uniformity of dosage unit, organic impuritiies and dissolution. The results indicated that Atorvastatin Calcium Tablets marketed in Thailand obtained satisfactory pharmaceutical characteristics. Keywords: atorvastatin calcium tablets, quality

Valsartan is an angiotensin II receptor blockers(ARBs) used to treat high blood pressure and heart failure. In 2018, the U.S. FDA recalled valsartan because of contamination of the carcinogenic chemicals called N-nitrosodimethylamine (NDMA). In Thailand, Thai FDA suspended the sale and collected both ARBs raw materials and finished products. A total of 232 samples which included losartan, valsartan, olmesartan, irbesartan, azilsartan, telmisartan and candesartan were sent to Department of Medical Sciences for the analysis of nitrosamines contamination (NDMA, N-nitrosodiethylamine; NDEA and N-nitroso-N-methyl-4-aminobutyric acid; NMBA, usingliquid chromatography-tandem mass spectrometry. It was found that Losartan rawmaterials are eight samples below the limit and five samples over the limit. Valsartan rawmaterials are three samples over the limit. Losartan finished products are four samples below the limit and forty-two samples over the limit. One-hundred and seventy samples of raw materials and finished products are free fromcontamination. The limits set by ICH for NDMA and NMBA are 96 ng while that of NDEA is 26.5 ng,based on the maximum daily dose. Thai FDA suspended the sale and their production thus patients can use the medicines with confidence and reduce unnecessary carcinogens risk. Keywords: antihypertensive drug, contamination, N-nitrosodimethylamine

Cannabis oral drops is the Cannabis extract in a suitable vegetable oil. It contains Cannabinoids, including Delta-9-tetrahydrocannabinol (Delta-9-THC) and/ or Cannabidiol (CBD). It is used for the treatment of intractable epilepsy, spasticity, nausea and vomiting. In present, the analytical method for this product is unavailable in the official pharmacopoeia. Thus, Bureau of Drug and Narcotic was necessary to developed and validated the method for determination of Delta-9-THC and CBD in Cannabis extract and Cannabis oral drops by High Performance Liquid Chromatography (HPLC). The chromatographic separation was accomplished on C18, 4.6 x 150 mm reverse-phase column. The linear gradient solutions consisted of mobile phase (A) Ammonium formate pH 3.75 with 10% acetonitrile and (B) 90% acetonitrile. The flow rate was maintained at 1.0 mL/min. The analytes were monitored at 228 nm. This method was specificity. The linearity range was obtained from 2 to 100 mcg/mL. The % recovery of accuracy of Delta-9-THC and CBD were in the range of 86-99 and 94-102%, respectively. The %RSD of repeatability and intermediate precision (different instruments and days) were not more than 2.0. The standard solution and sample solution were stable for at least 2 days. This developed method is suitable to use as standard method of Thai Pharmacopoeia for determination of Delta-9-THC and CBD in Cannabis extract and Cannabis oral drops. Keywords: Cannabinoids, Cannabis extract, Cannabis oral drops, HPLC

Bureau of Drug and Narcotic, Department of Medical Sciences is the sole organization in Thailand offering the proficiency testing of narcotics in urine specimens. The participating members comprise approximately 750 public and private laboratories. In the 2018 fiscal year, expenses incurred in relation to issuance of reports and relevant documents and postal services amounted to 220,000 Baht. Thus, information technology (IT) was implemented through a website of https://bdn.go.th/pt/ covering 4 programs of proficiency testing (drugs, psychotropics and narcotics as property in dispute, as well as narcotics in urine specimens). It has been found that, during a one year period, total operational costs of narcotics in urine analysis was drastically decreased by more than 140,000 Baht, equivalent to 64% cost reduction. In addition, not only time but also storage space were impressively reduced by greater than 80%. Ninety five percent of paper consumption was reduced leading to environmental friendliness. The financial breaking event could be achieved within only 2-3 years. Moreover, efficiency of confidentiality mechanism, data privacy, data transferring and evaluation have been hugely improved. This website is ready to cope with participants, networks and tests expansion in the near future. The self-tracking system can be performed by the participants themselves. Although customer satisfactory evaluation was excellent, the beneficial feedbacks and suggestions would be very important for further IT system improvement.

Urine drug testing process is an important step in screening drug users. To ensure that the test results are precise, accurate and reliable, it is therefore necessary that the laboratories testing should participate in the proficiency testing program with the certified unit according to ISO / IEC 17043: 2010. Bureau of Drugs and Narcotics, Department of Medical Sciences has been aunit of proficiency testing provider for narcotics in urine since the fiscal year 2003 until the present. The proficiency testing for narcotics in urine consists of two schemes, namely, scheme of screening test of narcotics in urine and confirmation testing of narcotics in urine.There are a number of participating laboratories in both the public and private sectors increased by 766 respectively in the fiscal year 2018. The prevalent narcotics, methamphetamine, morphine, marijuana, ecstasy and cocaine, were used as proficiency test samples four samples a year.Because of training courses and supervision the participating laboratories of us every year, the participants reported the accurate results increasing more than 90 percent in 2018. However, there are some members reported with the inaccurate test results therefore we will plan to develop such members further. Moreover, to meet the needs of members effectively, we have used information technology. Participants are satisfied with the service. Participants’ clientreceives fairness and increase the effectiveness of prevention and suppression of drug abuse in the country

Lamotrigine tablets is an antiepilepsy drugs, which is used as a monotherapy or with other medications to prevent and control seizures. It is also used as a mood stabilizers in bipolar disorders. Lamotrigine tablets formulations are available in the strength of 25, 50 and 100 mg. In the fiscal year 2018, Bureau of Drug and Narcotic cooperated with Thai Food and Drug Administration surveyed the quality of lamotrigine tablets by randomly collected samples from public hospitals, importers and local manufacturers under Quality Assurance of Medicine Program. The total of 31 samples, from 1 importer (3 registration numbers) and 2 manufacturers (6 registration numbers) were evaluated according to the United States Pharmacopeia specification (USP 40) for identification, assay, weight variation and organic impurities. The analytical method was verified prior to sample testing. The results showed that all samples (100%) complied with pharmacopeia specification. It can be concluded that lamotrigine tablets in Thailand have satisfactory pharmaceutical characteristics which will be used for drug procurement in hospitals. Key words : Lamotrigine tablets, Antiepilepsy drugs, Seizures, Mood stabilizers, Bipolar disorders

Illicit drugs are seized materials from lawsuit of action that non-accordance with Drugs Act, B.E. 2510 (1967). Identification of illicit drugs in seized materials is required by law. Bureau of Drug and Narcotic reviewed the illicit drug data during the fiscal year 2013 to 2016. A total of 301 cases, 2319 samples were evaluated in many dimensions, especially the type of legal and therapeutic use of drugs detected. All samples were received from government authorized consumer protection agency. The appearance of samples was more look like the modern drugs than the traditional drugs. In Identification data, most drugs were dangerous drugs, followed by specially-controlled drugs. In case of therapeutic use, the predominantly founded were drugs used for the treatment of erectile dysfunction, followed by drugs used in beauty injection products and drugs in other groups, respectively. These data showed that the many drugs were not to be used for treatment. The effective communication to consumer about drugs information may help reduce the problem of illicit drug. Key word : identification, illicit drugs, seized materials

Atropine sulfate injection and Norepinephrine bitartrate injection are drugs listed in the National List of Essential Medicines 2017 in the group of cardiovascular system drugs and antidotes. By intravenous administration, both of them were used for rescuing the patients in the case of cardiac arrest in intensive care unit (ICU). Therefore, their quality of them is important. Bureau of Drug and Narcotic perform the quality survey of Atropine sulfate injection in fiscal year 2017 and of Norepinephrine bitartrate injection in fiscal year 2018. The samples were collected from hospital and manufacturer via single window system. A total of 5 Atropine sulfate injection samples, classified into 1 registration 1 from manufacturer, a total of 13 norepinephrine bitartrate injection samples, classified into 4 registration from 4 importers, were evaluated for the content of active ingredient, pH determination, particulate matter, sterility test and bacterial endotoxins by using methods and specifications of the United States Pharmacopeia (USP39 and USP40 respectively). The analytical methods were verified for the suitability prior to sample testing. The results showed that all of samples are conformed to the requirement of all topics. It can be concluded that all of the samples surveyed are good quality. Keywords: quality, Atropine sulfate injection, Norepinephrine bitartrate injection

Montelukast is a selective leukotriene receptor antagonist. It is indicated for the prophylaxis and chronic treatment of asthma including the prevention of exercise-induced bronchoconstriction. In the fiscal year 2018, Bureau of Drug and Narcotic collaborated with Food and Drug Administration Thailand randomly collected samples from manufacturers, importers and hospitals under Quality Assurance of Medicine Program. A total of 24 samples with strength of 10 mg from one importer (1 registration number) and 3 local manufacturers (3 registration numbers) were evaluated according to the United States Pharmacopeia (USP40) for identification, assay, content uniformity and organic impurities. The analytical methods were verified prior to analysis. The survey showed that all samples complied with the USP40 specifications. It can be concluded that Montelukast sodium tablets have satisfactory pharmaceutical characteristics. Keywords: Montelukast sodium tablets, quality

Calcium carbonate tablets are used as calcium supplement for hypocalcemia patients such as acute and chronic hypoparathyroidism, postmenopausal women, osteoporosis, rickettsia and osteomalacia. In recent years, physicians also used for binding phosphate and maintain calcium balance in patients with chronic renal failure. In year 2016, Calcium carbonate tablets were selected by Bureau of Drug and Narcotic for quality survey. The samples were collected from public hospitals. Total of 40 samples from 9 companies, with 18 registration numbers at strength 350, 600, 625, 835, 1000, 1250, and 1500 mg were evaluated according to United States Pharmacopoeia 39 (USP 39). The tests were composed of identification, content of active ingredient, weight variation and dissolution. Two samples (5%) did not meet the requirement due to dissolution test. The results indicated that most of Calcium carbonate tablets have satisfactory quality. The summary report was published in GREEN BOOK which was distributed to government hospitals to be used for the procurement of drugs. Keyword : calcium carbonate tablets, quality

Black ginger (K. parviflora) was promoting as herbal Champion product. But there was a lack of reference standards for the quality control of raw materials, extracts and health products from Black ginger. For further step of herbal Department of Medical Sciences reference standards production, the isolation of three major compounds; DMF, TMF and PMF from Black ginger extract was studied by CC technique. TLC and UPLC-PDA-MS were used for identification. According to the results, the considered fraction (F4) containing three major compounds was obtained as 22.21% w/w of crude extract. After the separation of F4 fraction by flash column chromatography, TMF was isolated as 7.11% w/w of F4 and a combination fraction of DMF and PMF (F4-2) was obtained as 76.52% w/w of F4. Then the final step of column chromatograph was also operated for the separation of DMF from PMF as well. Based on this study, the isolation of these compounds is an efficient method in the production of herbal reference standards in the future. Keywords: Black ginger extract, Isolation, Major compounds

Clotrimazole is an imidazole antifungal drug which are available in various dosage forms such as creams, topical solutions and vaginal tablets. In the fiscal year 2018, the quality assessment of Clotrimazole was evaluated in accordance with the United States Pharmacopeia (USP 40). The method was verified prior to sample testing. A total of 176 samples were collected from public hospitals and manufacturers. 65 samples of creams were tested for assay and microbial examination. The results showed that 1 sample failed microbial examination. 6 samples of topical solutions were tested for assay, organic impurities and microbial examination and it was shown that 3 samples failed organic impurities. 105 samples of vaginal tablets were tested for assay, uniformity of dosage units, disintegration and organic impurities. The results showed that 52 samples failed organic impurities and disintegration. Keywords: Clotrimazole, tablets, solution, cream, quality

Disulfiram Tablet listed as class C in the National List of Essential Medicines 2018, and used for supporting the treatment of chronic alcoholism. For the reason that Disulfiram Tablet is classified as dangerous drug in the Medicine Act B.E. 2510 and its quality has never been studied before, so the quality survey of Disulfiram Tablet was performed by Bureau of Drug and Narcotic in the fiscal year 2018. The samples with strength of 500 mg were collected from the public hospitals by single window system. A total of 17 samples, 5 manufacturers 5 formulations from 11 manufacturers and 11 formulations in Thailand were evaluated for the content of active ingredient, weight variation and disintegration by using the methods and specifications of United States Pharmacopoeia (USP 40). The analytical methods were verified for the suitability prior to sample testing. The results found that all samples conformed to the requirement. It can be concluded that Disulfiram Tablet in Thailand have satisfactory qualities. These results may be beneficial to the hospital’s drug purchasing, customer’s drug selection and company for development pharmaceutical products. Keywords : disulfiram tablet, quality survey

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