盐酸曲马多注射液与盐酸布比卡因注射液在镇痛泵中的稳定性研究

目的 考察盐酸曲马多注射液与盐酸布比卡因注射液在镇痛泵中的稳定性.方法 采用高效液相色谱(HPLC)法测定配伍液中盐酸曲马多与盐酸布比卡因在72 h内的含量变化,并观察和检测配伍液的外观及pH值变化.结果 盐酸曲马多注射液与盐酸布比卡因注射液在0.9％氯化钠注射液中配伍后,在室温条件下放置72 h,盐酸曲马多与盐酸布比卡因的加样回收率分别为99.48％、100.20％,且配伍液无色澄明,pH无明显变化,两者的含量均＞98％,分别为100.16％和98.68％.结论 在室温条件下,盐酸曲马多注射液与盐酸布比卡因注射液在镇痛泵中72 h内均保持稳定.     

Stability of ondansetron hydrochloride in portable infusion-pump reservoirs.

The stability of ondansetron hydrochloride 0.24 and 2 mg/mL when delivered by portable infusion pump at near-body temperature over various time periods was investigated. Nine 100-mL drug reservoirs were prepared, three containing ondansetron hydrochloride 2 mg/mL and six containing ondansetron hydrochloride diluted with 0.9% sodium chloride injection to 0.24 mg/mL. Three of the reservoirs containing the diluted solution were refrigerated for up to 30 days at 3 degrees C before being attached to portable infusion pumps and pumped over 24 hours at 30 degrees C. The remaining six reservoirs were attached to pumps immediately after being filled, and the solutions were delivered for up to 24 hours (the diluted solution; three reservoirs) or up to seven days (the concentrated solution; three reservoirs) at 30 degrees C. Samples were taken initially and periodically and analyzed by high-performance liquid chromatography and with a pH meter. Both the diluted and the concentrated solutions of ondansetron hydrochloride retained at least 95% of the initial drug concentration under all the conditions studied. There was no appreciable change in pH. Ondansetron hydrochloride 0.24 mg/mL was stable when stored for up to 30 days at 3 degrees C and infused over 24 hours at 30 degrees C. Ondansetron hydrochloride 2 mg/mL was stable when infused for up to one week at 30 degrees C.     

Stability of morphine hydrochloride in a portable pump reservoir

The stability of morphine hydrochloride in an admixture with sodium chloride 0.9% injection in a portable pump reservoir was investigated. Duplicate samples containing morphine hydrochloride 0.5, 1.5 and 2.5 mg/ml were stored in original 100 ml plastic drug reservoirs at 32 °C for 60 days. An amount of 3 ml was removed immediately after preparation and at fixed intervals in the weeks after. All samples were tested for loss of vehicle, for appearance of precipitation and for change in colour or pH. Furthermore, they were analysed for drug concentration using high pressure liquid chromatography. No precipitation or change in colour was observed in any of the sample admixtures. There was no change in the pH values of any of the morphine hydrochloride concentrations from day 4 and later on. Only between day 1 and day 4 a slight, but not significant rise could be detected. There was no loss of morphine hydrochloride of any importance at any concentration in the samples over 60 days when corrected for loss of vehicle. Loss of vehicle (0.8±0.1 ml a week), on the other hand, gave a rise in morphine hydrochloride concentration.     

盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼在氯化钠注射液中的配伍稳定性研究

目的考察盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼在0.9%氯化钠注射液中的配伍稳定性。方法分别在4℃与25℃条件下,观察与检测盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼配伍液在0、4、8、24、48与72 h各时间点的外观、不溶性微粒数与p H变化,并采用高效液相色谱法测定配伍液中盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼在各时间点的相对百分含量变化。结果盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼配伍液在72 h内外观、不溶性微粒数及p H值均未见明显变化,各组分的相对百分含量均>98%。结论在4℃与25℃条件下,盐酸曲马多、枸橼酸芬太尼与盐酸托烷司琼在0.9%氯化钠注射液中72 h内均能保持稳定。     

Stability of fentanyl citrate in 0.9% sodium chloride solution in portable infusion pumps

The stability of fentanyl citrate diluted with 0.9% sodium chloride injection for use in portable infusion pumps was studied. The commercially available injection containing 50 micrograms of fentanyl per milliliter was diluted to a concentration of 20 micrograms/mL. Twelve 100-mL portions of the dilute solution were placed in polyvinyl chloride infusion pump drug reservoirs; six were stored at 3 degrees C and six at 23 degrees C; three at each temperature were overwrapped with polypropylene-Mylar. Initially and after 5, 10, 20, and 30 days of storage, 1-mL samples were taken from each reservoir, inspected for color change and precipitation, and assayed for fentanyl concentration by high-performance liquid chromatography. Initially and on day 30, pH of the samples was checked. No precipitation or change in color or pH was observed. No substantial decrease in fentanyl concentration was found in either the wrapped or unwrapped samples at either temperature, although concentrations on day 30 in the samples at 23 degrees C were slightly lower than those at 3 degrees C. Under the conditions studied, fentanyl citrate solutions containing 20 micrograms of fentanyl per milliliter can be stored for 30 days in polyvinyl chloride reservoirs for portable infusion pumps.     

盐酸曲马多与枸橼酸芬太尼在氯化钠注射液中的稳定性研究

目的考察盐酸曲马多与枸橼酸芬太尼注射液在0.9%氯化钠注射液中的配伍稳定性。方法在室温条件下,观察两药配伍后的外观及pH值变化,盐酸曲马多与枸橼酸芬太尼的含量测定采用SinoChrom ODS-BP色谱柱,以乙腈-0.05 mol/L磷酸二氢钾水溶液（25∶75）为流动相,流速为1.0 ml/min。结果配伍液中盐酸曲马多与枸橼酸芬太尼的含量均大于98%,72 h内外观与pH值均未见明显变化。结论在室温条件下,盐酸曲马多与枸橼酸芬太尼注射液在0.9%氯化钠注射液中72 h内保持稳定。     

Stability of morphine sulfate in portable pump reservoirs during storage and simulated administration

The stability of four concentrations of morphine sulfate injection in prefilled reservoirs for portable infusion pumps was studied after storage for 30 days at refrigerated and room temperature and after a three-day simulated administration period at body temperature. Thirty-milliliter samples of morphine sulfate injections in four concentrations--1, 5, 15, and 25 mg/mL--were loaded into a pump reservoir. The reservoirs were stored in the dark at 5 degrees C and 25 degrees C for 30 days. Samples were taken from each reservoir immediately after loading and after 7, 14, and 30 days of storage. The reservoirs were then connected to portable infusion pumps, which were run for three days at a flow rate of 0.4 mL/hr at 37 degrees C. The last sample was collected at the end of the three-day period. Samples were assayed for morphine sulfate content by high-performance liquid chromatography. The concentration of morphine sulfate increased up to 6% (for the 5-mg/mL sample) at refrigerated temperature and up to 16% (for the 15-mg/mL sample) at room temperature after 30 days' storage in the reservoirs. Evaporation of water from the reservoirs may have accounted for this phenomenon. No absolute relationship was found between the initial concentration of morphine sulfate and the percentage concentration increase after storage for 30 days. The change in morphine sulfate concentration before and after the three-day pumping period was not significant. Injectable solutions of morphine sulfate in concentrations ranging from 1 to 25 mg/mL are stable when stored at refrigerated temperature for 30 days in a prefilled drug reservoir.     

Effect of glucose 5% solution and bupivacaine hydrochloride on absorption of sufentanil citrate in a portable pump reservoir during storage and simulated infusion by an epidural catheter

The stability of sufentanil (5 g/ml as citrate) in admixtures with glucose 5% or bupivacaine hydrochloride (2 mg/ml) in 100 ml polyvinyl chloride portable pump reservoirs was investigated during simulated infusion by an epidural catheter at 32°C for 48 h and during storage at 4°C and 32°C for 30 days. During both experiments a small decrease (<5%) in concentration of sufentanil and bupivacaine was observed. No loss of sufentanil or bupivacaine could be detected (in both experiments) in the portable pump reservoirs when stored at 4°C for 30 days. A significant decrease of sufentanil was observed when stored at 32°C after 30 days when diluted with glucose (9.2%) or in combination with bupivacaine (8.9%); also, the bupivacaine concentration decreased significantly (4.7%). It is concluded that sufentanil in portable pump reservoirs can be used under patient conditions at 32°C for 7 days when diluted with glucose 5% or 3 days in combination with bupivacaine hydrochloride.     

Stability of bupivacaine hydrochloride with diamorphine hydrochloride in an epidural infusion

The stability of diamorphine (0.02 mg/ml as the hydrochloride) in 250 ml bupivacaine hydrochloride (0.15% wt/vol infusion) was studied by high pressure liquid chromatography at temperatures in the range 7 to 45°C. Diamorphine hydrochloride was degraded by approximately 0.13% per day at 7°C. No bupivacaine hydrochloride degradation was detectable during the study. The storage life of the combination at 7°C, based on the lower 95% confidence limit of the time to 5% diamorphine hydrochloride degradation, was 14 days. The stability at 25°C was adequate to allow transport and administration over 24 h at ambient temperature. Stability was also maintained for at least 24 h at 32 and 45°C. Infusion of the mixture with an ambulatory infusion pump which uses a standard polyvinyl chloride infusion bag is therefore possible. A study of its compatibility with different infusion pump medication reservoirs was not undertaken. The drugs were also stable on frozen storage at –18°C for up to 6 months.     

Stability of sufentanil citrate in a portable pump reservoir, a glass container and a polyethylene container

The stability of sufentanil citrate (100 ml, 5g/ml) in an admixture with sodium chloride 0.9% injection was investigated when filled in a portable pump reservoir with PVC wall, a glass container and a polyethylene container, at 32°C, 4°C and –20°C for up to 21 days. No change in colour was visually observed in any of the samples during the 21-day storage period. A slight precipitation was noticed in three out of nine portable pump reservoirs, one at each storage temperature. There was a slight rise in pH at each storage temperature in all samples. There was approximately 13% loss of sufentanil citrate in the portable pump reservoirs stored at 32°C during 2 days and 60% loss after 21 days, due to absorption of sufentanil citrate in the reservoir wall. No loss of sufentanil citrate could be detected in the portable pump reservoirs when stored at –20°C and 4°C. However, a serious inhomogeneity of the sufentanil citrate solution occurred after thawing at room temperature in the portable pump reservoirs which had been kept at –20°C. The homogeneity could be restored by shaking for approximately 10 min. There was no change in the sufentanil citrate concentrations in the glass containers and polyethylene containers stored at the three temperatures. The portable pump reservoirs stored at 32°C also showed a significant loss of vehicle due to evaporation (1.0±0.1 ml a week). This could not be detected in any of the other samples.     

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.     

Stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in portable pump reservoirs

The stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in prefilled drug reservoirs that were stored at -20 degrees C for 30 days, thawed at 5 degrees C for four days, and pumped at 37 degrees C for one day was studied. Each antimicrobial agent was diluted with sterile water for injection to a concentration representative of the most common dosage when administered via a portable infusion pump. Ten milliliters of each drug solution was placed in individual glass vials to serve as controls, and volumes appropriate to deliver the designated dosages were loaded into the drug reservoirs. Triplicate reservoirs were prepared for each drug. One-milliliter samples from all containers were taken on days 0, 30, 31, 32, 33, 34, 34.5, and 35. All solutions were observed for color change and precipitation. Drug concentrations were determined using high-performance liquid chromatography. Leaching of the plasticizer diethylhexyl phthalate (DEHP) was analyzed by packed-column gas chromatography on days 0 and 35. No color change or precipitation was observed. No DEHP concentrations above 1 ppm were detected. More than 90% of the initial concentrations of each drug remained, except penicillin G sodium, which had a mean concentration of 83.9 +/- 0.5% at the end of the study. Cefazolin sodium, cefoxitin sodium, and ceftazidime in admixtures with sterile water for injection are stable under the conditions of this study. Penicillin G sodium should not be administered for more than 12 hours after such a cycle of freezing and thawing.     

Stability of fentanyl citrate in glass and plastic containers and in a patient-controlled delivery system

This study determined the stability of fentanyl citrate stored in glass or polyvinyl chloride containers and the concentrations of fentanyl citrate delivered by the Janssen on-demand analgesic computer (ODAC) system. Solutions containing 500 micrograms of fentanyl citrate (10 mL) were added to 100-mL three glass containers each of 5% dextrose injection or 0.9% sodium chloride injection and to three 100-mL polyvinyl chloride containers of 5% dextrose injection or 0.9% sodium chloride injection. All containers were stored under usual light conditions and at room temperature. Samples were taken immediately and at 0.25, 0.5, 1, 6, 12, 24, 36, and 48 hours. To determine the concentration of fentanyl delivered via the ODAC system, fentanyl citrate injection 2500 micrograms (50 mL) was added to a 500-mL polyvinyl chloride bag containing 5% dextrose injection. The solution was connected to the ODAC system, and samples of bolus demand doses were collected at various times during a 30-hour period. All the samples were assayed by a stability-indicating gas-liquid chromatographic method. For both glass and plastic containers, the mean +/- S.D. recovery of fentanyl after 48 hours was 98.6 +/- 2.3% when the drug was diluted in 5% dextrose injection and 97 +/- 1.5% when the drug was diluted in 0.9% sodium chloride injection. There was no significant difference between the amount of fentanyl recovered from glass containers and the amount recovered from polyvinyl chloride containers. Nor was there any significant difference between the amount of fentanyl recovered from solutions containing 5% dextrose injection and the amount recovered from solutions containing 0.9% sodium chloride injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

美罗培南输液在便携式冷冻输液泵中的稳定性

目的 :研究美罗培南输液在输液泵中的稳定性。方法 :选用浓度为 2 0 ,30mg·ml-1的美罗培南输液 ,在两种条件下试验其在 2 4h内的稳定性。用高效液相色谱法测定药物浓度变化。结果 :两种浓度的美罗培南输液在两种条件下 ,2 4h内的浓度值变化率均小于 10 %。结论 :美罗培南输液在本试验的输液泵中 ,可稳定 2 4h。这对临床应用提供了依据。     

高效液相色谱法测定枸橼酸芬太尼注射液的含量

采用高效液相色谱外标法，以甲醇溶液（取甲醇４００ｍｌ，乙腈２００ｍｌ及冰醋酸０．６ｍｌ混匀）－０．２％无水硫酸钠的醋酸铵溶液（１→１００）（７：３）为流动相，检测波长２３０ｎｍ测定枸橼酸芬太尼注射液的含量，浓度在０．４～１．６μｇ范围内呈良好线性关系，相关系数ｒ＝０．９９９０，回收率为９９．９％，ＲＳＤ为１．４８％。     

反相高效液相色谱法测定复方明矾布比卡因注射液中盐酸布比卡因含量及有关物质

目的建立反相高效液相色谱法测定复方明矾布比卡因注射液的有关物质及盐酸布比卡因的含量。方法采用Diamonsil C18柱,以乙腈-磷酸盐缓冲液（取磷酸二氢钾1.94g,磷酸氢二钾2.48g,加水溶解并稀释至1 000mL,调节pH 6.8）（65∶35）为流动相;流速为1.0mL.min-1;有关物质检测波长为215nm,含量测定检测波长为263nm;柱温：30℃。结果在该色谱条件下,杂质峰与主峰均能有效分离,盐酸布比卡因在44.31～177.26μg.mL-1与峰面积线性关系良好（r2=0.999 7）;平均回收率为99.7%（n=9）,RSD=0.4%。结论本法简便、快速、准确,专属性好,可用于复方明矾布比卡因注射液的质量控制。     

Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate

This study assessed the absolute and relative bioavailabilities and transmucosal and gastrointestinal absorbency of fentanyl buccal tablet (FBT) and oral transmucosal fentanyl citrate (OTFC). In a randomized crossover design, 26 healthy subjects received FBT 400 microg (transmucosal), FBT 800 microg (oral), OTFC 800 microg (transmucosal), and fentanyl 400 microg (intravenous). The transmucosal FBT had the highest absolute bioavailability (0.65) compared with the oral FBT (0.31) or transmucosal OTFC (0.47). More fentanyl was absorbed transmucosally from FBT than OTFC (48% vs 22%). Median t(max) values were shorter following the transmucosal FBT (47 minutes) than the oral FBT (90 minutes) or the transmucosal OTFC (91 minutes). Transmucosal administration of FBT compared with dose-normalized OTFC resulted in higher total systemic fentanyl exposure, higher early systemic exposure, and higher C(max). The rate and extent of fentanyl absorption were greater following administration of FBT compared to OTFC. An approximately 30% smaller dose of FBT achieved systemic exposures comparable to OTFC.