Stability of morphine solutions in plastic syringes determined by reversed-phase ion-pair liquid chromatography

Hung, C.T.; Young, Michael; Gupta, Pramod

doi:10.1002/jps.2600770816

Cited by 22 publications

(10 citation statements)

References 34 publications

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“…(a) Azmorphine N-oxide; B=morphine; C=apomorphine; D=pseudomorphme. (b) A=solvent front; B=pethidic acid; C=meperidine.formation data were in agreement with published values(2,(15)(16)(17)(18). shows representative chromatograms of morphine, meperidine, and respective degradation products.…”

supporting

confidence: 90%

“…This summary indicates that stability information is often not specific and usually confined to stability studies of limited time duration. Only one study specified a shelf-life (2 It is questionable whether all quantitative analytical methods used to study the stability of morphine are stability-indicating. Morphine has been reported to undergo first-order degradation to form pseudomorphine as the primary degradation product, and morphine N-oxide and apomorphine as secondary products (2, 11).…”

Section: Introductionmentioning

confidence: 99%

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Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

et al. 1994

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Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candles), temperature (-20, 4 and 23 degrees C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were < or = 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. Shelf-life data indicate that morphine is stable for at least 6 weeks when protected from light.(ABSTRACT TRUNCATED AT 250 WORDS)

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supporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

et al. 1994

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“…For replicate HPLC injections the USP XXII requires a coefficient of variation of less than 2% (14). Our values of 1.34% and 1.95% for the within-day and between-day coefficients of variation are within this range and comparable to the results obtained by other investigators (12,19). These coefficients of variation are acceptable for stability testing of pharmaceutical preparations (20).…”

Section: Uv Spectroscopy and Hplc For Morphine Asscrysupporting

confidence: 90%

Stability of high-dose morphine chloride injection upon heat sterilization: comparison of UV-spectroscopy and HPLC

Steger

Martinelli

Mühlebach

1996

Journal of Clinical Pharmacy and Therapeutics

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Aarau, CH-5001 h r a u , Switzerland SUMMARYThe stability of a preservative-free morphine chloride solution for intravenous or intrathecal use manufactured at a concentration of 40 mglml, near the solubility limit in water, was studied. The influence of heat and oxygen on morphine content was measured with and without autoclaving, and after additional thermal and oxidative stress. The morphine injection was stable during steam sterilization at 121°C for up to I80 min if the solution was adjusted to a pH of 3. High-performance liquid chromatography with W detection (HPLC) and direct W spectroscopy (W) (the latter available in most hospital pharmacies for analytical purposes) were compared for specificity, precision and appropriateness for content and stability assessment of morphine solutions. UV could only be used for quantification of undecomposed morphine. Morphine degradation products of stressed solutions interfered with the direct W assay of morphine at 286 nm, whereas these interfering components were separated by the ion-pair reversed-phase HPLC used. The results demonstrate that even in the absence of stabilizers, morphine chloride solutions may safely be sterilized for 15 min at 121°C. The HPLC method was shown to be sufficiently sensi-

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“…The main breakdown product of morphine is pseudomorphine. 6 A solution of pseudomorphine (Tasmanian Alkaloids Pty Ltd) was prepared in mobile phase and injected into the HPLC system. Alfentanil stock solution 0.1% was mixed with…”

Section: Stability Indicating Capacitymentioning

confidence: 99%

Stability and Compatibility of Alfentanil Hydrochloride and Morphine Sulfate in Polypropylene Syringes

Sharley¹,

Burgess

2003

Pharmacy Practice and Res

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Aim: To establish the chemical stability and physical compatibility of alfentanil hydrochloride and morphine sulfate in polypropylene syringes for patient controlled analgesia at the Royal Adelaide Hospital. Method: A stability indicating high pressure liquid chromatography (HPLC) method was developed and validated. Concentrations of alfentanil hydrochloride and morphine sulfate stored in polypropylene syringes were measured over a sixmonth period. Sample syringes were stored under refrigeration (2‐8°C) and at room temperature (22±1°C). Visual inspection for macro particulate matter was undertaken using an Allen viewer. Stability was defined as maintaining at least 90% of the day zero concentration. Quality control standards were assayed on each study day to determine intra‐ and inter‐day precision and accuracy. Results: Morphine sulfate content remained at 99% of initial concentration after 182 days at both storage conditions. Alfentanil hydrochloride content remained at 100% of initial concentration after 182 days at both storage conditions. No particulate matter was visible in sample syringes throughout the study period. Conclusion: Alfentanil hydrochloride and morphine sulfate in polypropylene syringes are chemically stable and physically compatible for 180 days in the concentrations studied, when protected from light and stored either under refrigeration (2‐8°C) or room temperature (22±1°C). An expiry date of six months can be applied, facilitating efficient manufacturing and clinical evaluation in the management of acute pain.

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Stability of morphine solutions in plastic syringes determined by reversed-phase ion-pair liquid chromatography

Cited by 22 publications

References 34 publications

Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

Stability of high-dose morphine chloride injection upon heat sterilization: comparison of UV-spectroscopy and HPLC

Stability and Compatibility of Alfentanil Hydrochloride and Morphine Sulfate in Polypropylene Syringes

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