Is high titre ANA specific for connective tissue disease?

OBJECTIVE: A positive antinuclear antibody (ANA), while sensitive, is not specific for systemic lupus erythematosus or connective tissue diseases (CTD). The purpose of the present study was to review those sera with a high titre (> or = dilutions above screening) ANA and determine from a review of the charts if these higher titres offered a satisfactory specificity for CTD. METHODS: All FANA testing in this region is carried out in one of two related laboratories. We reviewed the medical records of patients who had a positive ANA at a titre 4 dilutions above screening at this city-wide laboratory over a 6-month period to determine whether this titre ("high titre") may offer relative diagnostic certainty. Antibodies to extractable nuclear antigens (ENA) and native DNA were also obtained. RESULTS: 422 ANA results were positive at high titre. The medical record was available for review in 320 patients, of whom 238 (75%) were seen by a specialist physician, almost always including a rheumatologist. Our review determined that 35% had a diagnosis of connective tissue disease, 21% had a diagnosis of a possible/probable inflammatory disease, 16% had an alternative specific diagnosis provided, and in 29% no final disease specific diagnosis was recorded but CTD was not suggested to us or the specialist by the data available. One or more anti-ENA antibodies and/or anti-DNA were positive in 69 (22%) and 8% of the sera tested respectively. CONCLUSION: While long term follow-up is still required, a significant proportion of patients with high titre ANA have no CTD at the time of testing. Setting a higher cutoff for reporting of ANA may not increase specificity sufficiently to make it a useful alternative or addition to reporting a positive or negative value at screening titre alone.

Photostability determination of commercially available nifedipine oral dosage formulations.

Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, undergoes photodegradation to dehydronifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydronifedipine (NDNIF) when exposed to sunlight. NIF photodegradation products do not contribute to clinical activity, thus the content of NIF must remain uniform between equipotent formulations. Large differences in light stability between bioequivalent NIF products could potentially result in the therapeutic failure of unstable preparations. Consequently, if large photostability differences do exist between NIF preparations, product substitution may not be warranted. The light stability of 10 intact immediate- or controlled-release oral NIF formulations, obtained from several European and North American manufacturers, was studied using direct continuous artificial sunlight exposure extending over a 12-week period. The content of both NIF and NDNIF for each product was measured to determine the extent of photodecomposition using a specific and sensitive reversed-phase high pressure liquid chromatographic (HPLC) method. In addition, NIF photodegradation was measured using both pure NIF powder and methanolic NIF solution to determine the effectiveness of the artificial sunlight source used in this study. After 12 weeks of artificial sunlight exposure, less than 3% of NDNIF (w/w initial NIF content) was present in each of the 10 tested dosage forms. Photodegradation was greater than 10% (w/w initial NIF content) in approximately 5-10 min (mean t1/2 = 31 min), and in approximately 24 h (mean t1/2 = 7.7 days) of artificial sunlight exposure for methanolic NIF solution and pure NIF powder samples, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereospecific high-performance liquid chromatographic assay of zopiclone in human plasma.

A high-performance liquid chromatographic (HPLC) assay for the analysis of the enantiomers of zopiclone (ZPC), a cyclopyrrolone hypnotic, in plasma was developed. Following the addition of chlordiazepoxide as internal standard (I.S.), plasma containing the ZPC enantiomers and I.S. was extracted by liquid-liquid extraction at an alkaline pH. After evaporation of the organic layer, the drug and I.S. were reconstituted in ethanol-hexane (80:20, v/v) and injected onto the HPLC column. The enantiomers were separated at ambient temperature on a 25-cm Chiralcel OD-H column with ethanol-hexane (60:40, v/v) as the mobile phase pumped at a flow-rate of 0.6 ml/min. The enantiomers of ZPC were quantified by fluorescence detection with excitation and emission wavelengths of 300 and 470 nm, respectively. The assay described allows for the direct quantitation of ZPC without pre-column derivatization, and is suitable for clinical studies of ZPC in humans after administration of therapeutic doses.

Sensitive high-performance liquid chromatographic assay for nifedipine in human plasma utilizing ultraviolet detection.

A rapid, simple, sensitive and selective reversed-phase high-performance liquid chromatographic (HPLC) technique is reported for the determination of nifedipine in human plasma. The procedure involves extraction of nifedipine from plasma under alkaline conditions (pH 12), separation via reversed-phase HPLC and ultraviolet detection (350 nm). The peak corresponding to nifedipine was free of interference from its photodegradation products or metabolites. The method was validated over the range 5-250 ng/ml nifedipine using weighted least-squares linear regression analysis. Accuracy and precision were within approximately 10% or less over the concentration range, except for the lowest concentration point which, nonetheless, was acceptable and approached 15%. The minimum quantifiable concentration of nifedipine was determined to be 5 ng/ml. The minimum detectable concentration was in the order of 1 ng/ml. Analysis of plasma samples collected from healthy volunteers demonstrate that this assay is applicable to clinical and pharmacokinetic studies.