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  1. Xue Qin QN, Ming LC, Abd Wahab MS, Tan CS, Yuda A, Hermansyah A
    Res Social Adm Pharm, 2023 Jun;19(6):873-881.
    PMID: 36914513 DOI: 10.1016/j.sapharm.2023.02.015
    INTRODUCTION: Dementia is a disorder that causes a decline of cognitive function, and it affects millions of people worldwide. Increased availability of medications used to treat dementia will inevitably increase the likelihood of drug-related problems (DRPs).

    OBJECTIVE: This systematic review sought to identify DRPs due to medication misadventures, including adverse drug reactions (ADRs), and use of inappropriate medications, among patients with dementia or cognitive impairments.

    METHODS: The included studies were retrieved from the electronic databases PubMed and SCOPUS, and a preprint platform (MedRXiv) which were searched from their inception through August 2022. The English-language publications that reported DRPs among dementia patients were included. The JBI Critical Appraisal Tool for quality assessment was used to evaluate the quality of studies included in the review.

    RESULTS: Overall, 746 distinct articles were identified. Fifteen studies met the inclusion criteria and reported the most common DRPs, which comprised medication misadventures (n = 9), such as ADRs, inappropriate prescription use, and potentially inappropriate medication use (n = 6).

    CONCLUSION: This systematic review provides evidence that DRPs are prevalent among dementia patients, particularly the older people. It indicates that medication misadventures such as ADRs and inappropriate drug use, as well as potentially inappropriate medications, are the most prevalent DRPs among older people with dementia. Due to the small number of included studies, however, additional studies are required to improve comprehension about the issue.

  2. Awang Jihadi MH, Yuda A, Sukorini AI, Hermansyah A, Shafqat N, Tan CS, et al.
    Explor Res Clin Soc Pharm, 2023 Dec;12:100348.
    PMID: 37885436 DOI: 10.1016/j.rcsop.2023.100348
    INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the non-communicable diseases which continues to rise in prevalence and mortality rate throughout the years. Drug-related problems (DRPs) are more prevalent among T2DM patients especially those with co-morbidities.

    OBJECTIVE: The objective of this study was to review and assess the prevalence and characteristics of DRPs among hospitalized type 2 diabetes mellitus patients.

    METHODS: The systematic review of the literature was carried out using five online databases: PubMed, Scopus, Google Scholar, Web of Science, and Cochrane Library from the inception of the database until June 2022. Studies included in the review were published in English or Malay language. The data were extracted and assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.

    RESULTS: A total of 939 studies were identified with 20 studies that met inclusion criteria and were included in this systematic review. The overall prevalence of DRPs in all 20 studies ranged from 7% to 94%. The most common DRPs included drug-drug interaction (DDI), adverse drug reaction (ADR), therapeutic effectiveness problems, and inappropriate medication use.

    CONCLUSION: The most common drug classes involved were antidiabetics (metformin), antihypertensives, antiplatelets and antibiotics. The risk factors contributing to DRPs included the presence of comorbidities, the number of medications, and polypharmacy. To conclude, the rate of DRPs incidence in hospitalized T2DM patients was observed to be high. Further future studies with appropriate study designs and methods of detecting DRPs will be necessary to reduce and prevent DRPs occurrences.

  3. Mohidin SRNSP, Moshawih S, Hermansyah A, Asmuni MI, Shafqat N, Ming LC
    J Evid Based Integr Med, 2023;28:2515690X231206227.
    PMID: 37822215 DOI: 10.1177/2515690X231206227
    Cassava (Manihot esculenta Crantz) is considered one of the essential tuber crops, serving as a dietary staple food for various populations. This systematic review provides a comprehensive summary of the nutritional and therapeutic properties of cassava, which is an important dietary staple and traditional medicine. The review aims to evaluate and summarize the phytochemical components of cassava and their association with pharmacological activities, traditional uses, and nutritional importance in global food crises. To collect all relevant information, electronic databases; Cochrane Library, PubMed, Scopus, Web of Science, Google Scholar, and Preprint Platforms were searched for studies on cassava from inception until October 2022. A total of 1582 studies were screened, while only 34 were included in this review. The results of the review indicate that cassava has diverse pharmacological activities, including anti-bacterial, anti-cancer, anti-diabetic, anti-diarrheal, anti-inflammatory, hypocholesterolemic effects, and wound healing properties. However, more studies that aim to isolate the phytochemicals in cassava extracts and evaluate their pharmacological property are necessary to further validate their medical and nutritional values.
  4. Juperi RNAA, Goh HP, Rehman IU, Lee KS, Ming LC, Hermansyah A
    J Pharm Policy Pract, 2023 Aug 24;16(1):101.
    PMID: 37620839 DOI: 10.1186/s40545-023-00594-5
    BACKGROUND: Pharmacy medicine (P) is obtained exclusively from a pharmacy under the supervision of a pharmacist. This study aims to understand the perception of healthcare professionals towards the dispensing separation, as well as the dispensing of pharmacy medicine by community pharmacies to enhance patient health outcomes in Brunei Darussalam.

    METHODS: A cross-sectional study was conducted between 1st March 2023 and 20th April 2023 among healthcare professionals. A newly designed and validated questionnaire was used. Its face and content validity, along with internal consistency, was adequately established. Convenient sampling was employed to recruit participants for the study. Statistical analysis using one-way ANOVA was performed, considering a p-value 

  5. Xuan YW, Goh HP, Rehman IU, Shafqat N, Al-Worafi YM, Ming LC, et al.
    J Pharm Policy Pract, 2023 Nov 29;16(1):162.
    PMID: 38031133 DOI: 10.1186/s40545-023-00609-1
    BACKGROUND: This study aimed to assess the general public's perception of services provided by community pharmacies, their willingness to utilize these services, their satisfaction with and understanding of community pharmacists, and their views on dispensing separation and pharmacy medicines (P medicines).

    METHODS: An online cross-sectional study was conducted, in which questionnaires were distributed among the general public. A novel questionnaire was designed and validated specifically for this study. It was composed of six sections: demographics, pharmacy usage and service preferences, understanding and satisfaction with pharmacists, views on dispensing separation, private community pharmacies, and knowledge of P medicines. Statistical analyses such as one-way ANOVA, independent t test, and binary logistic regression were employed, with a p value of 

  6. Al-Worafi YM, Goh KW, Hermansyah A, Tan CS, Ming LC
    JMIR Med Educ, 2024 Jan 12;10:e47339.
    PMID: 38214967 DOI: 10.2196/47339
    BACKGROUND: Artificial Intelligence (AI) plays an important role in many fields, including medical education, practice, and research. Many medical educators started using ChatGPT at the end of 2022 for many purposes.

    OBJECTIVE: The aim of this study was to explore the potential uses, benefits, and risks of using ChatGPT in education modules on integrated pharmacotherapy of infectious disease.

    METHODS: A content analysis was conducted to investigate the applications of ChatGPT in education modules on integrated pharmacotherapy of infectious disease. Questions pertaining to curriculum development, syllabus design, lecture note preparation, and examination construction were posed during data collection. Three experienced professors rated the appropriateness and precision of the answers provided by ChatGPT. The consensus rating was considered. The professors also discussed the prospective applications, benefits, and risks of ChatGPT in this educational setting.

    RESULTS: ChatGPT demonstrated the ability to contribute to various aspects of curriculum design, with ratings ranging from 50% to 92% for appropriateness and accuracy. However, there were limitations and risks associated with its use, including incomplete syllabi, the absence of essential learning objectives, and the inability to design valid questionnaires and qualitative studies. It was suggested that educators use ChatGPT as a resource rather than relying primarily on its output. There are recommendations for effectively incorporating ChatGPT into the curriculum of the education modules on integrated pharmacotherapy of infectious disease.

    CONCLUSIONS: Medical and health sciences educators can use ChatGPT as a guide in many aspects related to the development of the curriculum of the education modules on integrated pharmacotherapy of infectious disease, syllabus design, lecture notes preparation, and examination preparation with caution.

  7. Karuppannan M, Ming LC, Abdul Wahab MS, Mohd Noordin Z, Yee S, Hermansyah A
    J Pharm Policy Pract, 2024;17(1):2308617.
    PMID: 38420042 DOI: 10.1080/20523211.2024.2308617
    BACKGROUND: The safety, side effects and efficacy profile of COVID-19 vaccines remain subjects of ongoing concern among the public in Malaysia. The aim of this study was to determine the types of adverse effects following immunisation with COVID-19 vaccines and the differences based on various types of COVID-19 vaccines to raise public awareness and reduce vaccine hesitancy among the public.

    METHODS: A total of 901 Malaysian adults (≥18 years) who received various COVID-19 vaccines were selected to participate in our cross-sectional study through an online survey between December 2021 and January 2022.

    RESULTS: A total of 814 (90.3%) of the participants reported ≥1 side effect following COVID-19 immunisation. Of these, the predominant symptoms were swelling at the injection site (n = 752, 83.5%), headache (n = 638, 70.8%), pain or soreness at the injection site (n = 628, 69.7%), fatigue or tiredness (n = 544, 60.4%), muscle weakness (n = 529, 58.7%) and diarrhea (n = 451, 50.1%). Recipients of the Pfizer-BioNTech (Comirnaty ®) vaccine reported the highest number of adverse effects (n = 355, 43.6%), followed by mixed COVID-19 vaccines (n = 254, 31.2%), the Oxford-AstraZeneca (ChAdOx1-®[recombinant]) vaccine (n = 113, 13.9%) and the Sinovac (CoronaVac®) vaccine (n = 90, 11.1%). The study showed that individuals who reported significantly more side effects were of elderly age, female gender and high educational level [P value 

  8. Goh KW, Ming LC, Al-Worafi YM, Tan CS, Hermansyah A, Rehman IU, et al.
    Ann Med, 2024 Dec;56(1):2271942.
    PMID: 38346353 DOI: 10.1080/07853890.2023.2271942
    AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries.

    METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries.

    RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study.

    CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

  9. Ming LC, Azmi NHR, Goh HP, Chaw LL, Goh KW, Elkudssiah Ismail N, et al.
    Int J Environ Res Public Health, 2022 Aug 25;19(17).
    PMID: 36078298 DOI: 10.3390/ijerph191710584
    OBJECTIVES: The study aimed to measure the level of attitudes and the current practices of the female community in Brunei Darussalam regarding the usage of cosmetics.

    METHODS: An online survey was conducted using a non-probabilistic snowball sampling approach via the social media channels WhatsApp and Instagram. The inclusion criteria were female Bruneian citizens or permanent residents, aged between 18 and 65 years old, who can understand English or Malay, and use cosmetic products at least once a day.

    RESULTS: A total of 445 participants responded to the online survey. Most of the participants agreed that the use of cosmetic products improves one's physical appearance to the public (391, 87.8%) and also improves self-confidence (405, 91.1%). There were significant differences in monthly cosmetic product expenses and participants' attitudes about safe cosmetic use (p = 0.001). No significant changes in the individuals' attitudes based on their age or educational level were observed. Overall, the participants had a good level of cosmetic safety practice. Almost half of the participants use social media to obtain information regarding what cosmetics to use or purchase.

    CONCLUSION: There is a medium to high level of attitude and a high level of practice regarding the safe use of cosmetics among Bruneian female adults. Social media was the main source of information for the respondents, followed by friend circle and family members.

  10. Abdul Nasir HH, Goh HP, Wee DVT, Goh KW, Lee KS, Hermansyah A, et al.
    Int J Environ Res Public Health, 2022 Sep 09;19(18).
    PMID: 36141623 DOI: 10.3390/ijerph191811350
    BACKGROUND: Medication wastage is causing a cost burden to the healthcare system that is worth millions of dollars. An economic and ecological friendly intervention such as using a patient's own medications (POM) has proven to reduce wastage and save the cost spent by the hospital. The potential benefits of using POM in inpatient settings have yet to be explored in a country with universal health coverage. This study aimed to pilot test the POM intervention in an adult ward setting and to perform the economic analysis of using POM and ward stock during hospitalization.

    METHODS: A prospective cross-sectional observational study was conducted among the patients admitted to the medical and surgical wards in a public hospital located in Brunei Darussalam between February 2022 and April 2022. Hospitalized adults above 18 years old with regular medications with a minimum length of stay of 48 h and a maximum length of stay of 21 days were included in the study. These eligible patients were divided into a POM group and a non-POM group. The economic analysis of using POM was performed by calculating the direct cost per unit of medication used during admission (from unit-use, ward stock and POM) and comparing the cost spent for both groups. Expired ward stock deemed as medication wastage was determined. Medical research ethics were approved, and all participating patients had given their written informed consent before enrolling in this study.

    RESULTS: A total of 112 patients aged 63.2 ± 15.8 years participated in this study. The average cost of medication supplied by the inpatient pharmacy for the non-POM group was USD 21.60 ± 34.20 per patient, whereas, for the POM group, it was approximately USD 13.00 ± 18.30 per patient, with a mean difference of USD 8.60 ± 5.17 per patient (95% CI: -3.95, 27.47, p ≥ 0.05). The use of POM minimized 54.03% (USD 625.04) of the total cost spent by the hospital for the POM group within the period of the study.

    CONCLUSION: The pilot study showed that the supplied medication cost per patient was not significantly different between the POM and non-POM groups. Nevertheless, the utilization of POM during hospitalization is capable of reducing at least 50% of the total cost spent on inpatient medications by the hospital. The use of POM during hospitalization also helped in reducing the total time spent on the medication process per patient.

  11. Paneerselvam GS, Goh KW, Kassab YW, Farrukh MJ, Goh BH, Lua PL, et al.
    Front Med (Lausanne), 2023;10:992870.
    PMID: 37305144 DOI: 10.3389/fmed.2023.992870
    BACKGROUND: End-stage renal disease is the last stage of chronic kidney disease and can affect the quality of life (QOL) of dialysis patients. The aim of this study was to assess the quality of life and examine its determinants.

    METHODS: A cross-sectional survey involving patients on dialysis in a tertiary hospital was conducted from July 2020 to September 2020. Demographic data were collected using a predesigned questionnaire. QOL was measured using the 36-item KDQOL questionnaire, and statistical analysis was carried out using SPSS version 25.

    RESULTS: Of the 108 patients, 59 were men and 49 were women, and the mean age was 48.15 ± 15.4 years. The results showed that there was no significant difference in the mean score of all components of health-related quality of life in different types of dialysis. The demographic data, which included age, gender, ethnicity, marital status, education level, occupation, and monthly income, did not significantly affect the QOL of dialysis patients. Patients with a dialysis duration of more than 5 years had a better QOL compared to other groups. Laboratory parameters such as low albumin and low hemoglobin showed a significant correlation with the health-related quality of life of dialysis patients.

    CONCLUSION: The quality of life among patients on dialysis was impaired, especially in terms of burden of the kidney disease. Hypoalbuminemia and anemia were the two factors that influenced QOL.

  12. Belmehdi O, Taha D, Abrini J, Ming LC, Khalid A, Abdalla AN, et al.
    Biomed Pharmacother, 2023 Sep;165:115205.
    PMID: 37499451 DOI: 10.1016/j.biopha.2023.115205
    α-Hederin is a natural bioactive molecule very abundant in aromatic and medicinal plants (AMP). It was identified, characterized, and isolated using different extraction and characterization technologies, such as HPLC, LC-MS and NMR. Biological tests have revealed that this natural molecule possesses different biological properties, particularly anticancer activity. Indeed, this activity has been investigated against several cancers (e.g., esophageal, hepatic, breast, colon, colorectal, lung, ovarian, and gastric). The underlying mechanisms are varied and include induction of apoptosis and cell cycle arrest, reduction of ATP generation, as well as inhibition of autophagy, cell proliferation, invasion, and metastasis. In fact, these anticancer mechanisms are considered the most targeted for new chemotherapeutic agents' development. In the light of all these data, α-hederin could be a very interesting candidate as an anticancer drug for chemotherapy, as well as it could be used in combination with other molecules already validated or possibly investigated as an agent sensitizing tumor cells to chemotherapeutic treatments.
  13. Bouyahya A, Balahbib A, Khalid A, Makeen HA, Alhazmi HA, Albratty M, et al.
    Heliyon, 2024 May 15;10(9):e29718.
    PMID: 38694079 DOI: 10.1016/j.heliyon.2024.e29718
    Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.
  14. Shaik Mohamed Sayed UF, Moshawih S, Goh HP, Kifli N, Gupta G, Singh SK, et al.
    Front Pharmacol, 2023;14:1182937.
    PMID: 37408757 DOI: 10.3389/fphar.2023.1182937
    Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.
  15. El Menyiy N, Aboulaghras S, Bakrim S, Moubachir R, Taha D, Khalid A, et al.
    Biomed Pharmacother, 2023 Sep;165:115159.
    PMID: 37481929 DOI: 10.1016/j.biopha.2023.115159
    Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress and low-grade inflammation. Dietary antioxidants, including genkwanin, could decrease oxidative stress and the expression of pro-inflammatory cytokines or pathways. The present study is the first comprehensive review of genkwanin, a methoxyflavone found in several plant species. Indeed, natural sources, and pharmacokinetics of genkwanin, the biological properties were discussed and highlighted in detail. This review analyzed and considered all original studies related to identification, isolation, quantification, investigation of the biological and pharmacological properties of genkwanin. We consulted all published papers in peer-reviewed journals in the English language from the inception of each database to 12 May 2023. Different phytochemical demonstrated that genkwanin is a non-glycosylated flavone found and isolated from several medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia officinalis, and Leonurus sibiricus. In vitro and in vivo biological and pharmacological investigations showed that Genkwanin exhibits remarkable antioxidant and anti-inflammatory activities, genkwanin, via activation of glucokinase, has shown antihyperglycemic activity with a potential role against metabolic syndrome and diabetes. Additionally, it revealed cardioprotective and neuroprotective properties, thus reducing the risk of cardiovascular diseases and assisting against neurodegenerative diseases. Furthermore, genkwanin showed other biological properties like antitumor capability, antibacterial, antiviral, and dermato-protective effects. The involved mechanisms include sub-cellular, cellular and molecular actions at different levels such as inducing apoptosis and inhibiting the growth and proliferation of cancer cells. Despite the findings from preclinical studies that have demonstrated the effects of genkwanin and its diverse mechanisms of action, additional research is required to comprehensively explore its therapeutic potential. Primarily, extensive studies should be carried out to enhance our understanding of the molecule's pharmacodynamic actions and pharmacokinetic pathways. Moreover, toxicological and clinical investigations should be undertaken to assess the safety and clinical efficacy of genkwanin. These forthcoming studies are of utmost importance in fully unlocking the potential of this molecule in the realm of therapeutic applications.
  16. Aissa R, Ibourki M, Ait Bouzid H, Bijla L, Oubannin S, Sakar EH, et al.
    J Med Life, 2023 Jun;16(6):822-836.
    PMID: 37675158 DOI: 10.25122/jml-2022-0353
    Saffron, botanically known as Crocus sativus L., is renowned as the world's most expensive spice and has been utilized in various fields since ancient times. Extensive scientific research has been conducted on Crocus sativus (C. sativus), focusing on its phytochemical composition, diverse applications, and biological activities. C. sativus phytochemicals consist mainly of three compounds, namely crocin, picrocrocin, and safranal, which are responsible for most of its properties. Saffron is rich in bioactive compounds, more than 150 of which have been isolated. Owing to its unique composition and properties, saffron is used in various fields, such as the food industry, perfumery, cosmetics, pharmaceutics, and medicine. However, the high economic value of saffron makes it susceptible to adulteration and various fraudulent practices. To deal with this issue, a number of methods and techniques have been developed to authenticate and determine adulterants in saffron. This paper presents a bibliometric study of saffron based on the Web of Science database, analyzing 3,735 studies published between 2000 and 2021. The study also examined author participation and collaboration networks among countries. Production, transformation, chemical composition, methods of adulteration detection, uses, and health properties of saffron are also discussed.
  17. Loh GOK, Wong EYL, Goh CZ, Tan YTF, Lee YL, Pang LH, et al.
    Ann Med, 2023;55(2):2270502.
    PMID: 37857359 DOI: 10.1080/07853890.2023.2270502
    The study aimed to develop a sensitive and high-throughput liquid chromatography coupled with tandem mass spectrometry method to quantify concentrations of tramadol and paracetamol simultaneously in human plasma. Sample preparation involved single-step protein precipitation using methanol and two deuterated internal standards, tramadol D6 and paracetamol D4. Agilent Poroshell 120 EC-C18 (100 × 2.1 mm, 2.1 µm) analytical column was employed to achieve chromatographic separation. Detection was in positive ion multiple reaction monitoring mode. A tailing factor (Tf) of <1.2, separation factor (K prime) of >1.5 from the column dead time and signal-to-noise (S/N) ratio >10, were obtained for analytes and internal standards. The standard curve was linear over the concentration range of 2.5-500.00 ng/mL for tramadol and 0.025-20.00 μg/mL for paracetamol. A small injection volume of 1 µL, low flow rate of 440 µL/min and short analysis time of 3.5 min reduced the solvent consumption, analysis cost and system contamination. The results of method validation parameters fulfilled the acceptance criteria of bioanalytical guidelines. The method was successfully applied to a bioequivalence study of fixed-dose combination products of tramadol and paracetamol in Malaysian healthy subjects.
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