Long-term stability of diazepam injections.

Diazepam and its main degradation product 2-methyl-amino-5-chlorobenzophenon (MACB) were quantitatively determined by HPLC and spectrophotometry in one- to ten-years-old diazepam injections. The content of diazepam was within the specifications in all the samples. Not more than 1.5% degradation of diazepam was found after ten years.

The mechanism of particulate contamination in soft polyvinyl chloride infusion fluid bags.

In the seventies, it was shown that particles were generated in soft polyvinyl chloride (PVC) infusion fluid bags when they were shaken. In this investigation an exponentially modified log-normal distribution (EMLN) is fitted to the particle data. Using the formula for the volume of a sphere, the number-density distribution is converted into a volume-density distribution. The total particle load in the samples is estimated by integration for total particle volume. The results are expressed as volume concentration in plain SI-units (microliters/l). A four-factor analysis of variance demonstrates that the mechanism of the contamination process is most probably an emulsification of low molecular weight additives in the PVC plastic, i.e. di(2-ethylhexyl) phthalate (DEHP), epoxidized vegetable oils (EVO), and others.

The covariation of chemical contamination, particulate matter and turbidity in soft polyvinyl chloride infusion fluid bags.

About 200 samples of normal saline, isotonic glucose and Ringer acetate infusions in soft polyvinyl chloride (PVC) bags obtained from three manufacturers have been analyzed by conductometric particle counting, turbidimetry and gas liquid chromatography (GLC). The particle counts were fitted to an exponentially modified log-normal model and integrated for total particle-volume. Di(2-ethylhexyl) phthalate (DEHP) and epoxidized vegetable oils (EVO), which are the main water insoluble contaminants in PVC fluid bags, were determined by GLC. There was a strong linear correlation between turbidity and GLC results. The correlation between particle-volume concentration and the DEHP and EVO concentrations was fairly good. The results seem to verify that an emulsion of plastic additives is formed when soft PVC infusion fluid bags are shaken.

Racemization and oxidation in adrenaline injections.

Adrenaline injection fluids aged between 3 and 33 years were analyzed with respect to oxidation and racemization. The oxidation was determined by ion-pair reversed phase HPLC, and the degree of racemization was determined by derivatization of the adrenaline isomers to diastereomeric forms and subsequently separated by reversed phase HPLC. 10% adrenaline was oxidized after about 11 years, while 10% L-adrenaline was converted to D-adrenaline after only 4 years. After about 4 years, the injections contained less than 90% active adrenaline.

Determination by gas-liquid chromatography of trace amounts of soft polyvinyl chloride plastic additives in aqueous solutions. I. Epoxidized vegetable oils.

A gas-liquid chromatographic method for the determination of epoxidized vegetable oils (EVO), such as epoxidized soybean oil and epoxidized linseed oil, in aqueous solutions is described. The EVOs are extracted with n-hexane and transesterified to the methyl esters by sodium methoxide in methanol. 3% OV-210 is used as the stationary phase. The weakest standard solution corresponds to 5 micrograms/l (5 ppb) of EVO in an aqueous sample. The reproducibility of a single analysis is 5%. The method is used for the determination of EVO in intravenous fluids stored in flexible polyvinyl chloride bags.

Determination by gas-liquid chromatography of trace amounts of soft polyvinyl chloride plastic additives in aqueous solutions. II. Di(2-ethylhexyl) phthalate, epoxidized vegetable oils and stearates.

A method for the determination of di(2-ethylhexyl) phthalate (DEHP), epoxidized vegetable oils (EVO) and stearates in aqueous solutions is described. A stepwise extraction procedure is employed to separate DEHP and EVO from the stearates, using n-hexane as extraction solvent. EVO is transesterified to methyl esters by sodium methoxide in methanol. The stearates are derivatized by methanol containing sulfuric acid. The alkyl esters are analyzed by gas-liquid chromatography, using 3% OV-210 as the stationary phase. The concentrations of the weakest standard solutions correspond to 10, 5 and 8 micrograms/l (ppb) of DEHP, EVO and stearates, respectively, in the aqueous samples. The method is used for the determination of DEHP, EVO and stearates in intravenous solutions stored in flexible polyvinyl chloride bags.

The influence of product factors on the migration in soft polyvinyl chloride infusion fluid bags.

The concentration of epoxidized vegetable oils (EVO) and di(2-ethylhexyl) phthalate (DEHP) in infusion fluids in soft polyvinyl chloride (PVC) bags has been determined by gas-liquid chromatography prior to and after agitation. Normal saline, isotonic glucose and Ringer acetate from four different manufacturers were investigated. Agitation resulted in an increased concentration of EVO and DEHP. Significant differences in contamination level were observed between solutions of different compositions and in synonymous preparations from different manufacturers. The results indicated that the total amount of migrating EVO and DEHP was affected by the pH of the solution and by the age of the plastic material. It is suggested that the migration of EVO and DEHP during agitation is influenced by the concentration of plastic degradation products.

The influence of mono(2-ethylhexyl) phthalate and stearates on the migration in soft polyvinyl chloride infusion fluid bags.

The influence of mono(2-ethylhexyl) phthalate (MEHP) and stearates on the migration of di(2-ethylhexyl) phthalate (DEHP) and epoxidized vegetable oils (EVO) in soft polyvinyl chloride infusion fluid bags during agitation has been investigated by gas-liquid chromatography. Normal saline, isotonic glucose and Ringer acetate from 3 different manufacturers were investigated. A covariation was observed between the MEHP concentration in the solution and the pH. The MEHP concentration was not influenced by agitation. There was no correlation between the MEHP concentration in the solution and the migration of EVO and DEHP, or between the stearate concentration and the EVO and DEHP migration.

Migration of plastic additives from soft polyvinyl chloride bags into normal saline and glucose infusions.

Samples of soft polyvinyl chloride (PVC) fluid bags containing normal saline and glucose 50 mg/ml were analyzed for plastic additives. The bags were shaken for 24 hours before analysis. The PVC plastic materials contained di(2-ethylhexyl)phthalate, epoxidized vegetable oils and stearates as the main additives. The same components were found in the solutions. Mono(2-ethylhexyl)phthalate was detected only in the solutions.