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Biomedical subjects

N P J Day

Publications and source records attributed to N P J Day.

14 recordsLinked to original sources
PubMed2006

Identification of an isomer impurity in piperaquine drug substance.

A significant contaminant of the antimalarial drug piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]propane) has been identified using liquid chromatography-mass spectrometry (LC-MS) and 2D NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC). The impurity was identified as the positional isomer 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl]propane. The impurity is formed because of contamination of batches of 4,7-dichloroquinoline (a precursor in the synthesis of piperaquine) with 4,5-dichloroquinoline. The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%.

Antimalarials↗
PubMed2006

A simple and rapid liquid chromatographic assay for evaluation of potentially counterfeit Tamiflu.

A simple and rapid liquid chromatographic assay for the evaluation of potentially counterfeit oseltamivir (Tamiflu has been developed and assessed. The assay uses approximately 1mg Tamiflu powder when used for authentication and content estimate. The procedure was validated using 50 replicates analysed during five independent series with a total R.S.D. of 11.2%. The assay can also be used to monitor the exact content of oseltamivir in Tamiflu capsules. One Tamiflu capsule was transferred to a 250mL volumetric flask and 150mL water was added. The flask was placed in an ultrasonic bath at 40 degrees C for 20min to dissolve the capsule. The solution was allowed to cool to room temperature before the flask was filled up to the mark (250mL). A small aliquot was centrifuged and then directly injected into the LC-system for quantification. Oseltamivir was analysed by liquid chromatography with UV detection on a Hypersil Gold column (150mmx4.6mm) using a mobile phase containing methanol-phosphate buffer (pH 2.5; 0.1M) (50:50, v/v) at a flow rate of 1.0mL/min. The assay was implemented for the analysis of Tamiflu purchased over the Internet and at local pharmacies in Thailand and Vietnam.

Acetamides↗
PubMed2006

Predicting the clinical outcome of tetanus: the tetanus severity score.

OBJECTIVES: To create a new tetanus score and compare it with the Phillips and Dakar scores. METHODS: We used prospectively acquired data from consecutive patients admitted to the Hospital for Tropical Diseases, Ho Chi Minh City, to create the Tetanus Severity Score (TSS) with multivariate logistic regression. We compared the new score with Phillips and Dakar scores by means of resubstituted and prospective data, assessing performance in terms of sensitivity, specificity and area under receiver operator characteristic curves. RESULTS: Resubstitution testing yielded a sensitivity of 77% (298/385) and a specificity of 82% (1,183/1,437) for the TSS; 89% (342/385) and 20% (281/1,437) for the Phillips score; and 13% (49/385) and 98% (1,415/1,437) for the Dakar score. The TSS showed greatest discrimination with 0.89 area under the receiver operator characteristic curve (95% CI 0.88-0.90); this was 0.74 for the Dakar score and (95% CI 0.71-0.77) and 0.66 for the Phillips score (95% CI 0.63-0.70; P values <0.001). Prospective testing showed 65% (13/20) sensitivity and 91% (210/230) specificity for the TSS; 80% (16/20) and 51% (118/230) for the Phillips score; and 25% (5/20) and 96% (221/230) for the Dakar score. The TSS achieved the greatest area under TSS of 0.89 (95% CI 0.82-0.96), significantly greater than the Phillips score [0.74 (0.6-0.88), P = 0.049] but not the Dakar score [0.80, (0.71-0.90), P = 0.090]. CONCLUSIONS: The TSS is the first prospectively developed classification scheme for tetanus and should be adopted to aid clinical triage and management and as a basis for clinical research.

Adolescent↗
PubMed2005

A new approach to evaluate regression models during validation of bioanalytical assays.

The quality of bioanalytical data is highly dependent on using an appropriate regression model for calibration curves. Non-weighted linear regression has traditionally been used but is not necessarily the optimal model. Bioanalytical assays generally benefit from using either data transformation and/or weighting since variance normally increases with concentration. A data set with calibrators ranging from 9 to 10000 ng/mL was used to compare a new approach with the traditional approach for selecting an optimal regression model. The new approach used a combination of relative residuals at each calibration level together with precision and accuracy of independent quality control samples over 4 days to select and justify the best regression model. The results showed that log-log transformation without weighting was the simplest model to fit the calibration data and ensure good predictability for this data set.

Algorithms↗
PubMed2005

Development and validation of an automated solid phase extraction and liquid chromatographic method for the determination of piperaquine in urine.

A sensitive and specific bioanalytical method for determination of piperaquine in urine by automated solid-phase extraction (SPE) and liquid chromatography (LC) has been developed and validated. Buffered urine samples (containing internal standard) were loaded onto mixed phase (cation-exchange and octylsilica) SPE columns using an ASPEC XL SPE robot. Chromatographic separation was achieved on a Chromolith Performance RP-18e (100 mm x 4.6 mm I.D.) LC column with phosphate buffer (pH 2.5; 0.1 mol/L)-acetonitrile (92:8, v/v). Piperaquine was analysed at a flow rate of 3 mL/min with UV detection at 347 nm. A linear regression model on log-log transformed data was used for quantification. Within-day precision for piperaquine was 1.3% at 5000 ng/mL and 6.6% at 50 ng/mL. Between-day precision for piperaquine was 3.7% at 5000 ng/mL and 7.2% at 50 ng/mL. Total-assay precision for piperaquine over 4 days using five replicates each day (n = 20) was 4.0%, 5.2% and 9.8% at 5000, 500 and 50 ng/mL, respectively. The lower limit of quantification (LLOQ) was set to 3 ng/mL using 1 mL of urine, which could be lowered to 0.33 ng/mL when using 9 mL of urine and an increased injection volume.

Animals↗
PubMed2005

High throughput assay for the determination of piperaquine in plasma.

A high throughput assay for the determination of the antimalarial piperaquine in plasma has been developed and validated. The assay utilises 96-wellplate formats throughout the whole procedure, and easily enables a throughput of 192 samples a day using a single LC system. Buffer (pH 2.0; 0.05 M) containing internal standard was added to 0.25 mL plasma in a 96-wellplate (2 mL wells). The samples were extracted on a MPC solid phase extraction deep well 96-wellplate (3M Empore). Piperaquine and internal standard were analysed by liquid chromatography with UV detection on a Chromolith Performance (100 mm x 4.6 mm) column with a mobile phase containing acetonitrile-phosphate buffer (pH 2.5; 0.1 M) (8:92, v/v) at a flow rate of 3.0 mL/min. The within-day precisions for piperaquine were 3.3 and 2.3% at 40 and 1250 ng/mL, respectively. The between-day precisions for piperaquine were 5.8 and 1.3% at 40 and 1250 ng/mL, respectively. The total assay precisions using 29 replicates over 5 days were 6.7, 4.5 and 2.7% at 40, 200 and 1250 ng/mL, respectively. The lower limit of quantification (LLOQ) and the limit of detection (LOD) were 10 and 5 ng/mL, respectively using 0.25 mL plasma. Using 1 mL of plasma, it was possible to decrease LLOQ and LOD to 2.5 and 1.25 ng/mL, respectively.

Animals↗
PubMed2005

High throughput assay for the determination of lumefantrine in plasma.

A high throughput bioanalytical assay for the determination of lumefantrine in plasma has been developed and validated extensively. The within-day precisions for lumefantrine were 5.2, 3.5 and 2.5% at 200, 2000 and 15000 ng/mL, respectively. The between-day precisions were 4.0, 2.8 and 3.1% at 200, 2000 and 15000 ng/mL, respectively. The lower limits of quantification (LLOQ) and the limits of detection (LOD) were 25 and 10 ng/mL, respectively using 0.250 mL plasma. The average recovery of lumefantrine was 85% and independent upon concentration. The use of 96-well plate format and short chromatographic run has increased the daily sample throughput four times. The assay is particularly suitable for large therapeutic drug monitoring studies using day 7 sampling.

Antimalarials↗
PubMed2005

Development and validation of a solid-phase extraction-liquid chromatographic method for determination of amoxicillin in plasma.

A bioanalytic method for the determination of amoxicillin in plasma by hydrophilic interaction solid-phase extraction and liquid chromatography has been developed and validated. Plasma was precipitated with acetonitrile before samples were loaded onto a zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid-phase extraction column. Amoxicillin was analyzed by liquid chromatography on an Aquasil (150 x 4.6 mm) LC column with mobile-phase acetonitrile: phosphate buffer (pH 2.5; 0.1 mol/L) (7:93, v/v) and UV detection at 230 nm. A regression model using 1/concentration weighting was found the most appropriate for quantification. The intraassay precision for plasma was 3.3% at 15.0 microg/mL and 10.9% at 0.200 microg/mL. The interassay precision for plasma was 1.8% at 15.0 microg/mL and 7.5% at 0.200 microg/mL. The total-assay precision for plasma over 4 days using a total of 20 replicates was 13.2%, 5.5%, and 3.8% at 0.200 microg/mL, 3.00 microg/mL, and 15.0 microg/mL, respectively. The lower limit of quantification and the limit of detection were 0.050 microg/mL and 0.025 microg/mL, respectively, for 100 microL plasma. Long-term storage stability studies of amoxicillin in plasma indicate that a temperature of -80 degrees C is necessary to prevent degradation of amoxicillin.

Amoxicillin↗
PubMed2004

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials.

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.

Antimalarials↗
PubMed2003

Neuropathological assessment of artemether-treated severe malaria.

In animals, high doses of intramuscular artemether and artemotil have been shown to cause an unusual pattern of selective damage to certain brainstem nuclei, especially those implicated in hearing and balance. We aimed to investigate whether a similar pattern arises in human adults. We examined the brainstems of adults who died after treatment with high dose artemether or quinine for severe falciparum malaria for evidence of a pattern of selective neuronal damage. Neuropathological findings were similar in recipients of quinine (n=15) and artemether (n=6; total artemether doses received 4-44 mg/kg). No evidence was recorded for artemether-induced neurotoxic effects.

Adult↗
PubMed2002

Malaria in injection drug abusers in Vietnam.

A prospective case-control study was conducted in a referral hospital in Ho Chi Minh City, Vietnam, to compare the clinical and laboratory features and outcome of severe falciparum malaria in injection drug abusers (IDAs) with those of patients who had acquired malaria by mosquito bite. From 1991 to 1996, 70 IDAs were admitted to the hospital, of whom at least 32 had acquired malaria by needle sharing. Although IDAs were more likely than control patients with severe malaria to be malnourished and to have coincident hepatitis B, hepatitis C, and human immunodeficiency virus infections, the overall rates of mortality, complications, and recovery were similar in the 2 groups. The route of malaria acquisition did not affect the outcome of severe malaria. The management of severe malaria in IDAs is similar to that for other patients.

Adolescent↗
PubMed2002

The ica operon and biofilm production in coagulase-negative Staphylococci associated with carriage and disease in a neonatal intensive care unit.

Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in the neonatal intensive care unit (NICU). We evaluated the hypothesis that the ica operon and biofilm production are associated with CoNS disease in this setting. CoNS associated with bacteremia or blood culture contamination and from the skin of infants with CoNS bacteremia or healthy controls were obtained during a prospective case-control study on a busy NICU. A total of 180 strains were identified, of which 122 (68%) were Staphylococcus epidermidis and the remainder were S. capitis (n = 29), S. haemolyticus (n = 11), S. hominis (n = 9), S. warneri (n = 8), and S. auricularis (n = 1). The presence of the genes icaA, icaB, icaC, and icaD was determined by PCR, and biofilm production was examined using qualitative (Congo red agar [CRA]) and quantitative (microtiter plate) techniques. There were no significant differences in the presence of the ica operon or CRA positivity among the four groups of strains. However, quantitative biofilm production was significantly greater in strains isolated from either the blood or the skin of neonates with S. epidermidis bacteremia. We conclude that the quantity of biofilm produced may be associated with the ability to cause CoNS infection. This conclusion suggests that the regulation of biofilm expression may play a central role in the disease process.

Bacteremia↗
PubMed2002

Comparison of multilocus sequence typing and pulsed-field gel electrophoresis as tools for typing Staphylococcus aureus isolates in a microepidemiological setting.

Multilocus sequence typing (MLST) of Staphylococcus aureus is well suited to the study of global or long-term epidemiology, but its role in local epidemiology has not been defined. The present study has compared MLST with pulsed-field gel electrophoresis (PFGE) by using S. aureus isolates associated with carriage and disease in a busy regional renal unit. One hundred forty-four patients were prospectively recruited, of whom 103 were receiving hemodialysis and 41 were on continuous ambulatory peritoneal dialysis. Three nasal swab specimens were obtained 1 month apart on entering the study. A nasal swab was positive for S. aureus on at least one occasion in 50 patients (35%). Typing of the 104 carriage isolates demonstrated 21 PFGE types and 21 sequence types (STs). Thirty-one carriers had two or more positive nasal swabs; of these, the isolates in all swabs from a given carrier had identical PFGE types for 29 carriers; the isolates in all of the same 29 swabs had identical STs. The carriage strain in two patients changed both PFGE type and STs during the period of swabbing. Eight patients (6%) had an episode of S. aureus bacteremia during the 12-month study period, and two of these were nasal carriers. One of these invasive isolates had the same PFGE type and ST as the carriage isolate. There were no differences between Simpson's index of diversity for PFGE and Simpson's index of diversity for MLST for both invasive and carriage isolates, suggesting that the two methods have very similar discriminatory abilities. We conclude that PFGE and MLST performed equally in this study.

Adolescent↗