Fast and Sensitive HPLC-ESI-MS/MS Method for Etoricoxib Quantification in Human Plasma and Application to Bioequivalence Study.

Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation. The objective of the current study was to develop a sensitive, fast and high-throughput HPLC-ESI-MS/MS method to measure etoricoxib levels in human plasma using a one-step methanol protein precipitation technique. A tandem mass spectrometer equipped with an electrospray ionization (ESI) source operated in a positive mode and multiple reaction monitoring (MRM) were used for data collection. The quantitative MRM transition ions were m/z 359.15 > 279.10 and m/z 363.10 > 282.10 for etoricoxib and IS. The linear range was from 10.00 to 4000.39 ng/mL and the validation parameters were within the acceptance limits of the European Medicine Agency (EMA) and Food and Drug Analysis (FDA) guidelines. The present method was sensitive (10.00 ng/mL with S/N > 40), simple, selective (K prime > 2), and fast (short run time of 2 min), with negligible matrix effect and consistent recovery, suitable for high throughput analysis. The method was used to quantitate etoricoxib plasma concentrations in a bioequivalence study of two 120 mg etoricoxib formulations. Incurred sample reanalysis results further supported that the method was robust and reproducible.

Sample preparation and quantification of polar drug, allopurinol, in human plasma using LCMSMS.

A fast, selective and reproducible LC-MS/MS method with simple sample preparation was developed and validated for a polar compound, allopurinol in human plasma, using acyclovir as internal standard (IS). Chromatographic separation was achieved using Agilent Poroshell 120 EC-C18 (100 × 2.1 mmID, 2.7 µm) analytical column. The mobile phase was comprised of 0.1%v/v formic acid-methanol (95:05; v/v), at a flow rate of 0.45 mL/min. The effect of different protein precipitation agents used in sample preparation such as methanol, acetonitrile, a mixture of acetonitrile-methanol and a mixture of acetonitrile-acetone were evaluated to optimize the extraction efficiency of allopurinol and IS. The use of acetone-acetonitrile (50:50, v/v) as protein precipitating agent shortened the sample preparation time and improved the recovery of allopurinol to above 93%. The IS-normalised matrix factors at two concentration levels were 1.0, with CV of 5.1% and 4.2%. Allopurinol in plasma was stable at benchtop for 24 h, in autosampler tray for 48 h, in instrumentation room for 48 h, in freezer after 7 freeze-thaw cycles and in freezer for 140 days. Allopurinol stock standard solutions were stable for 140 days at room temperature and in the chiller. The short sample run time of the validated bioanalytical method allowed high throughput analysis of plasma samples in pharmacokinetic study of an allopurinol formulation. The robustness and reproducibility of the bioanalytical method was reaffirmed through incurred sample reanalysis (ISR).

Malaysia's Health Systems Response to COVID-19.

This study aimed to highlight the COVID-19 response by the Ministry of Health (MOH) and the Government of Malaysia in order to share Malaysia's lessons and to improve future pandemic preparedness. The team conducted a rapid review using publicly available information from MOH, PubMed, and World Health Organisation (WHO) Global Research on Coronavirus Disease Database to compile Malaysia's responses during the COVID-19 pandemic. Measures taken between 31 December 2019 and 3 June 2020 were classified into domains as well as the pillars described in the WHO COVID-19 Strategic Preparedness and Response Plan (WHO SPRP). Malaysia's response incorporated all pillars in the WHO SPRP and consisted of five domains, (i) whole-of-government, (ii) cordon sanitaire/lockdown, (iii) equity of access to services and supports, (iv) quarantine and isolation systems, and (v) legislation and enforcement. Some crucial measures taken were activation of a centralised multi-ministerial coordination council where MOH acted as an advisor, with collaboration from non-government organisations and private sectors which enabled an effective targeted screening approach, provision of subsidised COVID-19 treatment and screening, isolation or quarantine of all confirmed cases, close contacts and persons under investigation, with all strategies applied irrespective of citizenship. This was provided for by way of the Prevention and Control of Infectious Diseases Act 1988. A combination of these measures enabled the nation to contain the COVID-19 outbreak by the end of June 2020.

Impact of pharmacist insulin injection re-education on glycemic control among type II diabetic patients in primary health clinics.

BACKGROUND: Insulin injection technique re-education and diabetes knowledge empowerment has led to improved glycemic control. OBJECTIVES: To evaluate the impact of pharmacist's monthly re-education on insulin injection technique (IT), lipohypertrophy, patients' perception on insulin therapy and its effect on glycaemic control. METHODS: This randomized controlled, multi-centered study was conducted among type 2 diabetics from 15 government health clinics. 160 diabetics with baseline HbA1C ≥ 8% and unsatisfactory IT technique were randomized into control or intervention group. Control group received standard pharmacist counselling during initiation and at 4th month. Intervention group received monthly counselling and IT re-education for 4 months. Assessment of diabetes, IT knowledge, adherence and perception towards diabetes were conducted using validated study tools Insulin Treatment Appraisal Scale (ITAS) and Medication Compliance Questionnaire (MCQ)). RESULTS: 139 patients completed the study; control group (69), intervention group (70). In control group, all outcomes shown improvement except for patient's perception. Mean HbA1C decreased 0.79% ± 0.24 (p = 0.001). In intervention group, all outcomes improved significantly. HbA1c reduces significantly by 1.19% ± 0.10 (p < 0.001). Monthly re-education improved patient's perception towards insulin therapy (ITAS score reduced 1.44 ± 2.36; p = 0.021). Between groups, interventional arm shown significantly better improvement in all outcomes. Improvement was shown in IT technique (+2.02 score; p < 0.001), medication adherence (+1.48 score; p < 0.001) and ITAS (-1.99 score; p = 0.037). Mean HbA1C reduced an additional of 0.63% (p = 0.008) compared to control arm. CONCLUSION: Re-education is more effective in increasing adherence, reducing lipohypertrophy, improving injection technique and patient's perception on insulin therapy, thereby providing better glycaemic control.

A randomized single-dose, two-period crossover bioequivalence study of two fixed-dose Paracetamol/Orphenadrine combination preparations in healthy volunteers under fasted condition.

BACKGROUND: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia. METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%. RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%. CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably. TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.

Parenteral cytotoxic drug wastage at a tertiary hospital in Kuala Lumpur: How much and why?

PURPOSE: To identify the cost and reasons of returned parenteral chemotherapy regimens at a tertiary hospital in Kuala Lumpur, Malaysia. METHODS: Data were retrospectively extracted from all the Chemotherapy Return Forms in 2016, which is a compulsory documentation accompanying each return of parenteral chemotherapy regimen. The following data were extracted: patient's diagnosis, gender, location of treatment (i.e. ward/daycare clinic), start date of chemotherapy regimen, type of cytotoxic drug returned, dose of cytotoxic drug returned, number of cytotoxic drug preparations returned and reason for return as well as whether the returned cytotoxic drug preparations could be re-dispensed. The cost of wastage was calculated based on the cost per mg (or per unit) of the particular returned cytotoxic drug. RESULTS: One hundred and fifty-nine cases of returned chemotherapy regimen comprising of 231 parenteral cytotoxic drug preparations were analysed. The total cost of returned chemotherapy regimen for 2016 was €3632, with €756 (20.8%) worth of chemotherapy regimens returned due to preventable reasons and €2876 (79.2%) worth of chemotherapy regimens returned due to non-preventable reasons. Approximately 50% of cases returned chemotherapy regimen were due to deterioration of patient's clinical condition and another 24.5% of cases of returned chemotherapy regimen were attributed to adverse drug reactions. CONCLUSION: Wastage associated to non-preventable reasons such as adverse drug reactions and preventable causes like refusal of patients can be further reduced by using newer healthcare innovations and establishment of written institutional protocols or standard operating procedures as references for in-charge healthcare personnel when cytotoxic drug-related issues occur. Adoption of cost-saving strategies that have been proven by studies could further improve current cost containment strategies.