Micellar electrokinetic chromatography stability indicating assay and content uniformity determination for a cholesterol-lowering drug product.

This study describes a specific, linear, precise, accurate and sensitive method for the determination of a developmental cholesterol-lowering drug formulated in capsules. The method can also determine two known hydrolytic degradants of the drug. Samples are dissolved in acetonitrile-phosphate buffer pH 4.5, diluted with water and assayed by micellar electrokinetic chromatography (MEKC) in a buffer containing 0.1 M borate-0.025 M SDS at 30 degrees C with an applied voltage of 25 kV. Detection is by UV absorbance at 200 nm. The method was cross validated by comparison with a gradient elution HPLC method. The MEKC method gave at least equivalent precision, accuracy and sensitivity to HPLC but was superior in the resolution of the known impurities and gave a considerably shorter analysis time. The method has been accepted as part of a regulatory submission to the US Food and Drug Administration (FDA).

Construction and use of an inexpensive "anthropometer".

An inexpensive anthropometer, suitable for use in undergraduate projects, was constructed from aluminum rod and components designed from laboratory retort stands. Only modest workshop skills and widely available machine tools were required to produce the device, which could be used to take accurate and reproducible measurements of linear dimensions and the angles of orientation of body segments. Its use in student projects indicates the value of the angular measurements in investigating posture.

Investigation and optimisation of the use of micellar electrokinetic chromatography for the analysis of six cardiovascular drugs.

A micellar electrokinetic chromatography method was optimised for the separation of the six cardiovascular drugs atenolol, nicardipine, nifedipine, diltiazem, verapamil, and amlodipine by investigating the effects of pH, sodium dodecyl sulphate (SDS) concentration, selection and concentration of organic modifier. An electrophoresis buffer of 100 mM borate pH 8.1 containing 50 mM SDS and 15% (v/v) acetone was found to provide the optimum separation with respect to resolution and migration time.

The validation of analytical methods for drug substances and drug products in UK pharmaceutical laboratories.

Results of a survey on method validation of analytical procedures used in the testing of drug substances and finished products, of most major research based pharmaceutical companies with laboratories in the UK, are presented. The results indicate that although method validation shows an essential similarity in different laboratories (in particular, chromatographic assay methods are validated in a similar manner in most laboratories), there is much diversity in the detailed application of validation parameters. Testing procedures for drug substances are broadly similar to finished products. Many laboratories validate methods at clinical trial stage to the same extent and detail as at the marketing authorization application (MAA)/new drug application (NDA) submission stage, however, only a small minority of laboratories apply the same criteria to methodology at pre-clinical trial stage. Extensive details of method validation parameters are included in the summary tables of this survey, together with details of the median response given for the validation of the most extensively applied methods. These median response details could be useful in suggesting a harmonized approach to method validation as applied by UK pharmaceutical laboratories. These guidelines would extend beyond the recommendations made to date by regulatory authorities and pharmacopoeias in that minimum requirements for each method validation parameter, e.g. number of replicates, range and tolerance, could be harmonized, both between laboratories and also in Product Licence submissions.

Symmetry of radiological features in the wrist and hands of patients with early to moderate rheumatoid arthritis: a quantitative microfocal radiographic study.

Quantitative microfocal radiography was used to assess the degree of symmetry in radiological features between the dominant and non-dominant wrist and hands of 51 patients with early to moderately advanced RA. With few exceptions, erosion size and joint space width were bilaterally symmetrical between the dominant and non-dominant side in: total erosion area and total joint space width; area at each of the separate sites of erosion formation, and width at each joint space; and the change in these X-ray features over an 18-month study period. Asymmetry in the number and size of erosions and joint space occurred in a small number of patients within either extremity; these differences were not sustained over the study period. In view of this degree of bilateral symmetry, the extent and progression of the radiographic features in RA can be assessed from a single macroradiograph of either the left or right wrist and hand.

Quantitative microfocal radiography detects changes in erosion area in patients with early rheumatoid arthritis treated with myocrisine.

Patients with early rheumatoid arthritis (RA) were randomly divided into those receiving gold early (n = 13) or 6 months later (n = 10). They were followed 6 monthly over 18 months. Mean erosion area in gold and delayed gold, measured from macroradiographs, was comparable at baseline and increased significantly over the first 6 months. In the second 6 months, gold showed no increase and delayed gold an insignificant increase. By the third 6 months both groups showed a decrease. On comparing the second 6 months of gold therapy in gold and delayed gold with a group of patients with RA of similar disease duration (n = 34) not receiving gold, a lower proportion (p < 0.005) had erosion area progression and a higher proportion (p < 0.001) erosion repair.

The effects of cisapride on gastro-oesophageal reflux in children with and without neurological disorders.

Cisapride was used to treat gastro-oesophageal reflux in seven children with neurodevelopmental disorders and in 15 children who were neurologically normal. 24-hour lower-oesophageal pH monitoring was carried out before and after treatment. The neurologically normal group had a statistically significant decrease after treatment in percentage time pH less than 4, but children with neurological abnormalities did not have a comparable improvement in reflux scores.

Erosion number and area progression in the wrists and hands of rheumatoid patients: a quantitative microfocal radiographic study.

Microfocal radiography has been used to evaluate the relation between erosion number and erosion area in the hands and wrists of 51 patients with early to moderately advanced rheumatoid arthritis. The hands of these patients showed different patterns of erosion progression, in terms of the relation between changes in number and area, and included those showing a decrease in one or both of the erosion parameters. The mean number of erosions in the group increased between the first and second visits. By the third visit (a mean of 48 months from the onset of symptoms) the mean number of erosions in the wrist and hand of the group had approached a constant value of 75 erosions. Over the same period the mean erosion area of the group continued to increase. Measurement of changes in erosion area is a more sensitive indicator of erosion progression than erosion number, both within the group and in individual patients.