Stability of esmolol hydrochloride and sodium nitroprusside in intravenous admixtures

The stability of esmolol hydrochloride and sodium nitroprusside in an admixture containing both drugs was studied. Solutions containing sodium nitroprusside in a final concentration of approximately 200 micrograms/mL and esmolol hydrochloride in a final concentration of 10 mg/mL in 5% dextrose injection were prepared in a 250-mL volumetric flask. The flask was wrapped with a light-protective cover, stored at ambient room temperature (15-30 degrees C), and protected from light. All experiments were conducted in triplicate with samples taken at 0, 2, 4, 8, and 24 hours. Testing included measurement of pH and absorbance at 400 and 600 nm. High-performance liquid chromatography was used to measure esmolol hydrochloride and sodium nitroprusside concentrations. No changes were observed in the physical appearance, pH, or absorbance of the admixtures. Neither the esmolol hydrochloride nor the sodium nitroprusside concentrations varied by more than 4% during the study. Under the conditions studied, esmolol hydrochloride is compatible with sodium nitroprusside in an admixture containing both drugs.     

Stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures.

The stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures was studied. Admixtures of amrinone and digoxin were studied at one concentration. Amrinone admixtures with propranolol hydrochloride, sodium bicarbonate, potassium chloride, and verapamil hydrochloride were studied at two concentrations. In general, 0.45% sodium chloride injection was used as the diluent; 5% dextrose injection was also used for the procainamide hydrochloride experiments. Duplicate solutions of each test admixture and single-drug control admixture were prepared and stored for four hours at 22-23 degrees C under fluorescent light. Samples were analyzed by visual inspection, tested for pH, and assayed by high-performance liquid chromatography. Admixtures containing amrinone 1.25 or 2.5 mg/mL (as the lactate salt) and sodium bicarbonate 37.5 mg/mL precipitated immediately or within 10 minutes. No changes in pH or visual appearance were noted for amrinone admixtures with procainamide hydrochloride, digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Appreciable degradation of both amrinone and procainamide was observed after four hours when the two were mixed in 5% dextrose. No degradation of amrinone or procainamide was seen when the 5% dextrose was replaced by 0.45% sodium chloride. Amrinone and sodium bicarbonate were incompatible in intravenous admixtures. Amrinone was compatible with digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Amrinone and procainamide were compatible in 0.45% sodium chloride injection but not in 5% dextrose injection.     

Stability of esmolol hydrochloride in the presence of aminophylline, bretylium tosylate, heparin sodium, and procainamide hydrochloride

The visual and chemical compatibility of esmolol hydrochloride mixed with aminophylline, heparin sodium, bretylium tosylate, or procainamide hydrochloride in 5% dextrose injection was studied. Esmolol hydrochloride 600 mg was injected into polyvinyl chloride bags containing 100 mL of 5% dextrose injection with aminophylline 100 mg, heparin sodium 5000 units, bretylium tosylate 100 mg, or procainamide hydrochloride 400 mg. All admixtures were prepared in triplicate and stored at room temperature under fluorescent light. Esmolol concentrations were measured with high-performance liquid chromatography at 0, 2, 4, 8, and 24 hours. Samples were also examined for precipitate formation and pH and color changes by using visual, microscopic, and spectrophotometric methods. No detectable changes in color or pH and no particulate formation were observed in any of the sample bags. Esmolol concentrations varied by less than 5% throughout the 24-hour study period. Esmolol hydrochloride was visually compatible and chemically stable for at least 24 hours when mixed with aminophylline, heparin sodium, bretylium tosylate, or procainamide hydrochloride in polyvinyl chloride bags containing 5% dextrose injection.     

Stability of ranitidine hydrochloride in total nutrient admixtures

The stability of ranitidine hydrochloride in total nutrient admixtures (TNAs) containing 5% intravenous fat emulsion was studied. A TNA containing lipids and glucose was prepared aseptically in three ethylene-vinyl acetate bags. Ranitidine hydrochloride 100 mg and 200 mg was added to two of the bags to yield concentrations of 50 micrograms/mL and 100 micrograms/mL, respectively. The third bag served as a control. At 0, 12, 24, 48, and 72 hours, the ranitidine content was measured by high-performance liquid chromatography, the pH of the admixtures was determined, and the bags were visually inspected for signs of color changes, creaming, or precipitates. Particle-size distribution was measured at 72 hours and compared with that in the control bag at time zero. No appreciable changes in pH occurred over 72 hours, and no visual changes were observed. At concentrations of 50 and 100 micrograms/mL of admixture, ranitidine hydrochloride activity declined approximately 80% during the study period. Approximately 10% of the initial concentration was lost in 12 hours. In both cases, there was no variation in particle-size distribution compared with that in the control bag at time zero. Ranitidine hydrochloride appears to be stable for up to 12 hours at room temperature in the admixtures studied, and the lipid emulsion apparently was not altered during this period by ranitidine.     

Interaction of poly-2-methyl-5-vinyl-N-ethylpyridinium bromide and heparin studied by means of ultraviolet and infrared spectroscopy

Antithrombotic properties are induced in polymers used in vascular surgery by modifying their surface chemically by introducing heparin by means of quaternary bases. The authors have studied the interaction of heparin with quaternary polyvinylpyridinium bromide. Optimal conditions for obtaining this complex have been established. The complex is insoluble in distilled water but passes partly into solution in the presence of an excess of heparin or in physiologic solution. Using spectral methods and elementar analysis it was found that the interaction of heparin with quaternary polyvinylpyridinium gives rise to a polyelectrolyte complex in which heparin undergoes structural changes, probably pertaining to sulfonamide or sulfoether groups.     

Interaction of aztreonam with nafcillin in intravenous admixtures

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

HPLC-ECD法测定盐酸多巴胺预灌装注射液的含量

目的建立测定盐酸多巴胺预灌装注射液含量的HPLC-ECD方法。方法采用Diamonsil-C18柱(250 mm×4.6 mm,5μm),以0.11%庚烷磺酸钠溶液(含0.1 mmol/L EDTA-2Na及5%冰醋酸,用1 mol/L NaOH溶液调节pH值至3.4)-甲醇(70∶30,v/v)为流动相,玻碳电极为工作电极,银/氯化银电极为参比电极,工作电位为+0.65 V,流速1.0 ml/min,柱温20℃。结果盐酸多巴胺在0.05～5μg/ml浓度范围内线性关系良好(r=0.999 9,n=5),平均加样回收率为(99.19±4.03)%(n=3),日内及日间RSD均小于4%(n=3);3批样品中盐酸多巴胺的平均含量相当于标示量的(102.97±1.11)%。结论该方法准确、快速、灵敏度高,能够用于盐酸多巴胺预灌装注射液的含量测定。     

Stability of amiodarone hydrochloride in admixtures with other injectable drugs

The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.     

HPLC法测定盐酸索他洛尔氯化钠注射液中盐酸索他洛尔的含量

目的应用HPLC法测定盐酸索他洛尔氯化钠注射液中盐酸索他洛尔的含量。方法色谱柱为依利特Kromaisl C18（5μm,4.6 mm×250 mm）,流动相为乙腈-0.2%庚烷磺酸钠溶液（21∶79）（用磷酸调节pH至3.0）,流速为1.0 ml/min,检测波长为228 nm,柱温为室温。结果盐酸索他洛尔在0.081~0.324 mg/ml范围内,浓度与峰面积线性关系良好（r=0.9999）;平均回收率为98.76%,RSD为0.97%（n=9）。精密度试验RSD为0.78%（n=6）。结论该方法测定结果准确、灵敏、可靠。     

Stability of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate admixtures

A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate, and the stability of the three drugs mixed together in four infusion fluids was assessed. Solutions were prepared with two concentrations of the three drugs similar to those administered intrathecally. Admixtures were prepared in Elliott's B solution, 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection. and lactated Ringer's injection. Solutions were filtered and kept in a disposable syringe in a 25 degrees C water bath for 24 hours. An HPLC assay capable of separating the three drugs and their degradation products was developed and validated. With one exception, all three drugs were stable in all four solutions for 24 hours. Hydrocortisone sodium succinate concentrations decreased to less than 90% of initial concentration in one of the admixtures with Elliott's B solution. No precipitation was noted in any admixture during the first eight hours of storage, but longer storage led to precipitation of unknown substances in some solutions. Admixtures of these three drugs in the four solutions tested are stable for at least 10 hours at 25 degrees C. However, intrathecal and administration of such admixtures within several hours of preparation is encouraged since none contains antibacterial preservatives.     

Compatibility of aminophylline and methylprednisolone sodium succinate intravenous admixtures

The stability of aminophylline and methylprednisolone sodium succinate in admixtures containing both drugs was studied. Admixtures containing aminophylline 1.0 mg/mL and methylprednisolone sodium succinate 2.0 and 0.5 mg/mL were prepared in both 5% dextrose injection and 0.9% sodium chloride injection. Each admixture was prepared in triplicate and samples were kept at room temperature in glass. Immediately after admixture and at one, two, and three hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The admixtures had higher pH values after aminophylline was added, but pH of the samples did not change significantly. Aminophylline concentrations did not change significantly throughout the study period. In 0.9% sodium chloride admixtures with methylprednisolone sodium succinate 0.5 mg/mL, less than 90% of the initial methylprednisolone concentration remained at two hours at the 2.0 mg/mL initial concentration, less than 90% remained at three hours. However, methylprednisolone alcohol (a pharmacologically active form of methylprednisolone sodium succinate) was detected in increasing concentrations after the first hour. Aminophylline in a final concentration of 1.0 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2.0 mg/mL or less in 5% dextrose injection or 0.9% sodium chloride injection and administered intravenously within three hours after mixing.     

电导法测定肝素钠中硫酸基含量

目的建立一种测定肝素钠中硫酸基含量的方法。方法将肝素钠通过阳离子交换树脂转变为肝素酸,用氢氧化钠进行滴定,通过电导率的变化确定滴定终点,对硫酸基进行定量分析。结果硫酸基的平均加样回收率为99.36%,RSD为1.15%。结论此法简便准确,重复性较好。     

Interaction of non-steroidal anti-inflammatory drugs, etoricoxib and parecoxib sodium, with human serum albumin studied by fluorescence spectroscopy

The mechanism of interaction of the non-steroidal anti-inflammatory drugs, etoricoxib and parecoxib sodium, with human serum albumin (HSA) was studied using fluorescence spectroscopy. There was only one class of binding site with association constants of the order of 10(4). Thermodynamic parameters suggest that van der Waals and hydrogen bonding interactions in the case of etoricoxib, and electrostatic and hydrogen bonding interactions in the case of parecoxib sodium, are predominantly involved in the binding. Studies in the presence of the hydrophobic probe, 1-anilinonaphthalene-8-sulfonate (ANS), showed that hydrophobic interactions are not involved in the binding of these drugs to HSA. Displacement studies using the site-specific probe, dansylsarcosine piperidinium salt (DSS), showed that the drugs are bound at site II on the HSA molecule. However, etoricoxib and parecoxib sodium are bound at different regions within site II. Increase of pH and the presence of salt caused significant changes in the association constants and the concentration of free pharmacologically active drug. Stern-Volmer analysis of the binding data indicated that the tryptophan residues of albumin are not fully accessible to anionic parecoxib sodium and a predominantly static quenching mechanism is operative in each case.     

Compatibility of premixed theophylline and methylprednisolone sodium succinate intravenous admixtures

The stability of theophylline supplied as a premixed injection and of methylprednisolone sodium succinate in admixtures containing both drugs was studied. Solutions containing theophylline in concentrations of 4.0 mg/mL and 0.4 mg/mL were used. Methylprednisolone sodium succinate was added to each solution to produce a final concentration of 0.5 mg/mL and 2.0 mg/mL of methylprednisolone alcohol, a pharmacologically active form of methylprednisolone sodium succinate. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass containers. Immediately after admixture and at 3, 6, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol content. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of theophylline in 5% dextrose injection to the methylprednisolone sodium succinate solutions resulted in decreased pH values for all solutions, which did not vary significantly throughout the study period. Theophylline concentrations did not change significantly compared with baseline. In solutions containing theophylline 0.4 mg/mL with either 2.0 or 0.5 mg/mL of methylprednisolone sodium succinate, less than 90% of the initial methylprednisolone sodium succinate concentrations remained at 24 hours. However, within three hours after admixture preparation, methylprednisolone alcohol was detected in those solutions in increasing concentrations. A commercial preparation of premixed theophylline in 5% dextrose injection in a concentration of 4 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2 mg/mL or less and administered intravenously within 24 hours after mixing.     

反相高效液相色谱法测定盐酸索他洛尔氯化钠注射液的含量

目的采用高效液相色谱法,测定盐酸索他洛尔氯化钠注射液中盐酸索他洛尔的含量.方法色谱柱:Shim-pack C18150mm×4.6mm;流动相:甲醇-水-冰醋酸-三乙胺(17:87:0.11:0.13);流速:1mL/min;检测波长:228nm.结果注射液测定无干扰.盐酸索他洛尔在浓度9.27～92.7μg/mL(r=0.9998)范围内线性关系良好;平均回收率100.6%,RSD=1.7%.结论本法准确、简便、可靠,样品中其它物质对主药测定无干扰.     

反相高效液相色谱法测定盐酸洛美沙星氯化钠注射液中洛美沙星的含量

目的：建立盐酸洛美沙星氯化钠注射液中洛美沙星含量的测定方法。方法：高效液相色谱法,色谱柱菲罗门Gemini-C18（250 mm×4.6 mm,5μm）,流动相：以戊烷磺酸钠溶液（取戊烷磺酸钠1.5 g,磷酸二氢铵3.5 g,加水950 ml使溶解,用磷酸调节pH值至3.0,用水稀释至1 000 ml）-甲醇（65∶35）为流动相,检测波长为287 nm。结果：在10.0～199.5μg/ml范围内,洛美沙星色谱峰峰面积与其浓度成良好线性关系（r=1.000 0）,平均回收率为100.11%,RSD为0.51%（n=9）。结论：本方法简便、准确、重现性好,可用于盐酸洛美沙星氯化钠注射液的质量控制。     

Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection

The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures.     

Cardiovascular dopamine receptors: role of renal dopamine and dopamine receptors in sodium excretion

Research efforts in the area of peripheral dopamine have now established the presence of two distinct subtypes--DA1 and DA2--of DA receptors, and have identified a potential role for dopamine produced within the kidney in the control of renal sodium excretion. Selective DA1 and DA2 receptor agonists are being developed because they exhibit therapeutic potential for treatment of cardiovascular and renal disorders. Furthermore, basic research efforts are aimed towards identifying the stimulus and/or stimuli for the production of dopamine within the kidney and characterizing the cellular signalling processes involved in mediating the renal effects of dopamine and selective DA receptor agonists.     

四苯硼钠法测定盐酸苯乙双胍片含量的研究

本文利用在酸性条件下，苯乙双肌与四苯硼钠1：1定量沉淀，研究了四苯硼钠法测定其含量的方法，片剂的回收率为99.2 0．53％。本法简便、快速、准确、重现性好，测得结果与中国药典法[2]一致，可用于盐酸苯乙双肌片的含量测定。