Shift work, parental cardiovascular disease and myocardial infarction in males.

Background: Shift work has been associated with an increased risk of cardiovascular disease (CVD). However, there is a need for more studies to determine whether there is an interaction between shift work and other risk factors of CVD, thereby increasing the risk of CVD in shift workers. Aims: To discern whether shift work and parental mortality from myocardial infarction (MI) or sudden cardiac death (SCD) interact to increase the risk of MI in men. Methods: A case-control dataset was used to assess interaction between shift work and parental history of CVD, using death from MI or SCD, or death before age 65, on an additive scale. Results were reported as relative excess risk due to interaction, attributable proportion due to interaction (AP) and synergy index (SI). Results: There was an interaction between shift work and paternal mortality from MI or SCD, when both factors were present [SI = 2.39; 95% confidence interval (CI) 1.02‒5.6 and AP = 0.4; 95% CI 0.08‒0.73]. Conclusions: Paternal mortality from MI or SCD interacts with shift work to increase the risk of MI in men.

Determination of drugs by direct injection of plasma into a biocompatible extraction column based on a protein-entrapped hydrophobic phase.

Drugs were determined by direct injection of plasma samples into a biocompatible extraction column. The column is based on particles with a biocompatible external surface and a hydrophobic internal surface. The pores of the particles are small enough to exclude the protein molecules; the drug molecules can penetrate the porous particle and are retained on the hydrophobic internal surface. Biocompatibility of the particles was obtained by reaction of the external surface with the human plasma protein alpha1-acid glycoprotein. The surface within the pores of the particles contains hydrophobic C8 or C18 groups. The biocompatible extraction column was used in a fully automated system for the determination of ibuprofen, naproxen, propranolol, carbamazepine and phenytoin in plasma. No pressure increase was observed during the analysis of several hundred plasma samples. Plasma concentrations of propranolol in the range 4.5-125 ng/ml were determined with a precision (R.S.D.) of 0.75-1.8%. Linear calibration graphs were observed for the five drugs, and correlation coefficients of 1.0000 were obtained for four of the five model compounds.

Optimization of the separation of enantiomers of basic drugs. Retention mechanisms and dynamic modification of the chiral bonding properties on an alpha 1-acid glycoprotein column.

The chromatographic properties of 29 basic drugs were studied by varying the pH and the concentration of inorganic ions in the mobile phase. It was observed that the chromatographic performance of most hydrophobic basic drug compounds could be strongly enhanced by decreasing the pH in the mobile phase from 7 to 4-6. The enantioselectivity increased and a much faster resolution was obtained. The results indicate that ion exchange and ion-pair distribution may be involved in the retention process of cationic drug enantiomers. Increasing the concentration of acetate and phosphate increases the retention of the enantiomers of the drug compounds. The relative contribution of the two retention processes can be affected by the pH and the nature and the concentration of the ions in the mobile phase. Decreasing the pH reduces the influence of the ion-exchange process since the negative charge of the protein is decreased. The enantioselectivity is also greatly affected by increasing salt concentration.

Direct injection of large volumes of plasma/serum on a new biocompatible extraction column for the determination of atenolol, propranolol and ibuprofen. Mechanisms for the improvement of chromatographic performance.

Very large volumes of serum/plasma can be directly injected to a new extraction column based on particles with a biocompatible outer surface and C18 groups within the pores. The biocompatibility has been obtained by attaching the human plasma protein alpha 1-acid glycoprotein to the outer surface of the particles. The pores are small enough to exclude the plasma protein molecules. Atenolol and propranolol were extracted on the extraction column as ion-pair with octanesulfonic acid as the counterion. The same counterion was used in the analytical mobile phase. A strong improvement of the recovery can be obtained using octanesulfonic acid as counterion in the extraction mobile phase. The recovery of atenolol increased from about 53.5% to about 93.4% using octanesulfonic acid as counterion. The chromatographic performance was also strongly affected by chromatography of the basic drugs as ion-pair with octanesulfonic acid. The improvement was due to trapping in a smaller section of the extraction column and enrichment of the drug on top of the analytical column. The enrichment was due to the transfer of the analyte to the analytical column in a zone with high concentration of counterion. Furthermore, the sample zone is compressed during the migration on the analytical column. The compression effect was caused by the counterion zone, migrating in front of the sample zone, giving the analyte higher retention on the front side than on the back side of the sample zone. Displacement of protein bound drug (ibuprofen) by addition of octanoic acid, was tested in order to study the influence on the recovery and the effect on the chromatographic performance. The recovery was improved and the chromatographic performance was greatly improved. The improvement obtained on the separation efficiency of ibuprofen was due to enrichment on top of the analytical column and compression during the migration through the analytical column. The enrichment was caused by a reduction of pH in the sample--octanoic acid zone transferred from the extraction column. The octanoic acid zone migrated in front of the sample zone giving a lower pH in front of the ibuprofen zone than behind. Thus, higher retention occurred in front of than behind the sample zone, which gave rise to compression. The methods developed for atenolol, propranolol and ibuprofen could be used for the determination of serum/plasma concentrations after single doses of the drugs with very high accuracy and precision. Linear calibration graphs were obtained and the r values were > or = 0.9999.

Reversed-phase ion-pair chromatography of tetracycline, tetracycline analogs, and their potential impurities.

Methods are presented for the separation of tetracycline, tetracycline analogs, and their potential impurities by reversed-phase ion-pair chromatography. The mobile phase consisted of a phosphate buffer with tripropylamine or N,N-dimethyloctylamine as counterions and acetonitrile as the organic modifier. The chromatographic properties of the tetracyclines were significantly improved by addition of the tertiary amines. The best result was obtained with N,N-dimethyloctylamine as the counterion, which gave good separation efficiency and peak symmetry for most of the substances studies. Addition of the tertiary amines to the mobile phase also significantly affected the capacity factors of the tetracyclines. Stability studies of the tetracyclines showed a fast degradation of chlortetracycline to isochlortetracycline and of lymecycline to tetracycline in phosphate buffer solutions of different pH. The purity of pharmaceutical preparations of tetracyclines was also investigated.U

Identification of 15-hydroperoxyabietic acid as a contact allergen in Portuguese colophony.

15-Hydroperoxyabietic acid (15-HPA) has been isolated from Portuguese colophony of the gum rosin type and identified as its methyl ester. The structure of the compound was elucidated using UV, IR, NMR and mass spectrometry. 15-HPA methyl ester was found to be an elicitor when tested in colophony-sensitized guinea-pigs. The sensitizing capacity was verified in the same species and 15-HPA methyl ester was considered to be a strong allergen. The eliciting potential was also verified in patients with known allergy to colophony. The Portuguese gum rosin investigated contained approximately 1% of 15-HPA. Based on its allergenicity and the amounts isolated, we conclude that 15-HPA is a main contact allergen in Portuguese gum rosin.

Rapid determination of tetracycline and lumecycline in human plasma and urine using high-performance liquid chromatography.

A rapid and accurate method for the determination of tetracycline in human plasma and urine is presented. Determination of tetracycline in plasma is based on precipitation of plasma proteins with trifluoroacetic acid, followed by injection of the centrifuged plasma sample onto a muBondapak C18 column. Acetonitrile in phosphate buffer pH 2.2 is used as mobile phase. Only tetracycline, and no trace of lumecycline can be detected in plasma and urine after administration of lumecycline, indicating that lumecycline is completely degraded to tetracycline, lysine and formaldehyde in the gastrointestinal tract prior to absorption. Determination of tetracycline in urine was performed by injection of urine diluted with phosphoric acid onto a muBondapak Phenyl column. The precision of determination of tetracycline in plasma, expressed as the relative standard deviation, was less than 3% at tetracycline concentrations of 0.05 and 3.7 micrograms/ml. Urine determinations were made with a precision of less than 1.5% at tetracycline concentrations of 0.5 and 6.7 micrograms/ml.

Comparison between two methods for the determination of the total and free (R)- and (S)-disopyramide in plasma using an alpha 1-acid glycoprotein column.

Two different high-performance liquid chromatographic systems for the determination of the total and free (R)- and (S)-disopyramide (DP) in plasma and urine were compared. In method I a Nucleosil C8 column was coupled in series with an alpha 1-acid glycoprotein column. Method II consisted of two systems; a LiChrosorb Si 60 column was used for the determination of the racemic drug concentration and the R/S ratio was determined on an alpha 1-acid glycoprotein column. The recovery of (R)- and (S)-DP from plasma was greater than 97% in both methods. The precisions of the (R)- and (S)-DP determinations in plasma are high with both methods. The relative standard deviations for the determination of the free concentration do not exceed 6.5% at 1.59 micrograms/ml racemic DP. Method II is preferred as it can also be used to determine the concentration of (R)- and (S)-monodesisopropyramide. It is also easier to avoid disturbances from endogenous compounds in plasma samples with method II than with method I. It was observed that DP was incorporated into urine sediment during storage. A simple ultrasonic treatment of the urine samples was demonstrated to release DP from the sediment.

Bioanalysis of diclofenac as its fluorescent carbazole acetic acid derivative by a post-column photoderivatization high-performance liquid chromatographic method.

A sensitive and selective bioanalytical liquid chromatographic method for diclofenac is described. The drug was detected as a flourescent derivative, which was demonstrated by 1H NMR and mass spectrometric studies to be carbazole acetic acid. Diclofenac was derivatized by UV irradiation of the substance performed as a post-column photoreaction. The reactor was a PTFE capillary wound around a 254-nm UV lamp. Diclofenac was isolated from the plasma samples by precipitation of the proteins with acetonitrile. A 50-microliters volume of the supernatant was injected onto a Nucleosil C18 column. The mobile phase was 32% acetonitrile in pH 6.6 buffer. Carbazole acetic acid was detected by a fluorescence detector using an excitation wavelength of 288 nm and an emission wavelength of 360 nm. The recovery was 92%, the standard curve was linear in the range 10-5500 ng diclofenac per ml plasma, and the relative standard deviation at 10 and 5000 ng of diclofenac per ml plasma was 9.0% and 3.3%, respectively. The limit of detection was 6 ng/ml at an injection volume of 50 microliters. Chromatograms of human and rat plasma containing diclofenac are shown.