Oxytocin preparation stability in several common obstetric intravenous solutions

Gard, John W; Alexander, J.; Bawdon, Roger E.; Albrecht, Jon T.

doi:10.1067/mob.2002.121104

Cited by 17 publications

(18 citation statements)

References 3 publications

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“…The stability of OT in most common infusion solutions has been extensively studied, and in recent papers a stabilizing effect of divalent metal ions in citric acid buffers was demonstrated . Surprisingly, neither the structural features favoring chemical degradation in solution, nor the degradation mechanism, nor the identity of the degradation products, have been described in the literature.…”

Section: Introductionmentioning

confidence: 99%

On the mechanism of degradation of oxytocin and its analogues in aqueous solution

Wiśniewski¹,

Finnman²,

Flipo³

et al. 2013

Biopolymers

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Oxytocin (OT) is a cyclic nonapeptide containing one internal disulfide bond between its Cys(1) and Cys(6) residues. Although OT is one of the most commonly used peptidic drugs, the mechanism of its degradation in aqueous solution and the identity of its degradants have not been fully elucidated. To investigate the pathways and products of OT degradation in slightly acidic to neutral solutions, we prepared the peptides: OT, [D-Cys(1)]OT, a series of N-alkylated OT analogues, [[(13)C3,(15) N]Cys(1)]OT, and OT where each sulfur atom was systematically replaced by either methylene, (34)S, or Se. The peptides were incubated at 40°C and the degradation products studied by HPLC, LCMS, and (13)C-NMR. Our findings suggest that the degradation begins with β-elimination of the disulfide linkage to form a putative intermediate linear peptide containing an S-thiocysteine (a persulfide) in position 6 and a dehydroalanine in position 1. This intermediate persulfide appears to donate a sulfur atom to an intact OT molecule to form OT trisulfide and higher monomeric polysulfides, while the dehydroalanine residue is hydrolyzed with loss of the N-terminal amino group to yield a linear N-pyruvoylated octapeptide containing a reduced Cys(6). Based on the MS and (13)C-NMR data of the products from degradation of [[(13)C3,(15)N]Cys(1)]OT, we postulate that the ultimate degradation products of OT are dimers composed of two pyruvoylated octapeptides held together by one disulfide bridge between the two Cys(6) residues and by one more, non-reducible, linkage resulting from an aldol-type condensation between the two N-terminal pyruvoyl groups.

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Section: Introductionmentioning

confidence: 99%

On the mechanism of degradation of oxytocin and its analogues in aqueous solution

Wiśniewski¹,

Finnman²,

Flipo³

et al. 2013

Biopolymers

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“…While concentrations ≤ 80U/1000cc (i.e., ≤40 units/500cc) have been demonstrated to be stable for at least 7 days (and therefore a premixed bag can have a shelf-life of 7days), no such data are available for the 80U / 500cc concentration. 25–26 As a result, hospital pharmacies will typically accord no more than a 2-day shelf-life for premixed oxytocin concentration greater than 40 units in 500cc. Therefore, stability studies of high dose oxytocin regimens are needed to facilitate its efficient clinical use and evaluation.…”

Section: Discussionmentioning

confidence: 99%

Higher-Dose Oxytocin and Hemorrhage After Vaginal Delivery

Tita

Szychowski

Rouse

et al. 2012

Obstetrics & Gynecology

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Objective Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage following cesarean delivery. We compared two higher-dose regimens (80U and 40U) to our routine regimen (10U) among women who delivered vaginally. Methods In a double-masked randomized trial, oxytocin (80U, 40U or 10U) in 500ml was given over 1 hour after placental delivery. The primary outcome was a composite: any treatment of uterine atony or hemorrhage. Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6% or greater in hematocrit. A sample size of 600 per group (N=1800) was required to compare each of the 80U and 40U to the 10U group. At planned interim review (n=1201), enrollment in the 40U group was stopped for futility and enrollment continued in the other groups. Results Of 2,869 women, 1,798 were randomized: 658 to 80U, 481 to 40U and 659 to 10U. Most characteristics were similar across groups. The risk of the primary outcome in the 80U group (6%; RR 0.93, 95% CI: 0.62–1.40) or the 40U group (6%; 0.94, 0.61–1.47) was not different compared with the 10U group (7%). Treatment with additional oxytocin after the first hour was less frequent with 80U compared with 10U (RR 0.41; 0.19–0.88) as was a 6% or greater decline in hematocrit (0.83; 0.69–0.99); both outcomes declined with increasing oxytocin dose. Outcomes were similar between the 40U and 10U groups. Conclusion Compared with 10 units, 80 or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when given in 500ml over 1 hour for vaginal delivery. Eighty units decreased the need for additional oxytocin and the risk of a 6% or greater decline in hematocrit.

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“…There are some published studies in the literature that do report the short-term stability of oxytocin (3,6). Gard et al (3) have reported oxytocin is stable in lactated Ringer's solution and lactated Ringer's-dextrose 5% solution over a 24-hour period at 25°C and over a 7-day period at 5°C.…”

Section: Discussionmentioning

confidence: 99%

“…There are few studies which provide the guidance regarding the short-term stability of these compounded syringes (3,6). In a study by Boothby et al (7), the stability of oxytocin solution was examined in Ringer's lactate solution at 4 and 25°C for over 31 days.…”

Section: Introductionmentioning

confidence: 99%

“…It is commonly used in the clinical settings for the induction and augmentation of the first stage of labor, mid trimester abortion, and the cessation or prevention of postpartum hemorrhage (1)(2)(3)(4). The recommended doses of oxytocin are as follows; for the induction of labor: 10 units per 1,000 mL, for the control of post-partum bleeding: 10 to 40 units per 1,000 mL, and for the treatment of inevitable absorption: 10 units in 500 mL (5).…”

Section: Introductionmentioning

confidence: 99%

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Stability-indicating HPLC method for the determination of the stability of oxytocin parenteral solutions prepared in polyolefin bags

2012

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Oxytocin is very commonly used in clinical settings and is a nonapeptide hormone that stimulates the contraction of uterine smooth muscles. In this study the stability of extemporaneously compounded oxytocin solutions was investigated in polyolefin bags. The sterile preparations of oxytocin were compounded to the strength of 0.02 U/mL in accordance with United States Pharmacopeia (USP) <797> standards. In order to carry out the stability testing of these parenteral products, the solutions were stored under three different temperature conditions of −20°C (frozen), 2-6°C (refrigerated), and 22-25°C (room temperature). Three solutions from each temperature were withdrawn and were assessed for stability on days 0, 7, 15, 21, and 30 as per the USP guidelines. The assay of oxytocin was examined by an HPLC method at each time point. No precipitation, cloudiness or color change was observed during this study at all temperatures. The assay content by HPLC revealed that oxytocin retains greater than at least 90% of the initial concentrations for 21 days. There was no significant change in pH and absorbance values for 21 days under all the conditions of storage. Oxytocin parenteral solutions in the final concentration of 0.02 U/mL and diluted in normal saline are stable for at least 30 days under frozen and refrigerated conditions for 30 days. At the room temperature, the oxytocin solutions were stable for at least 21 days. The stability analysis results show that the shelf-life of 21 days observed in this study was far better than their recommended expiration dates.

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Oxytocin preparation stability in several common obstetric intravenous solutions

Cited by 17 publications

References 3 publications

On the mechanism of degradation of oxytocin and its analogues in aqueous solution

On the mechanism of degradation of oxytocin and its analogues in aqueous solution

Higher-Dose Oxytocin and Hemorrhage After Vaginal Delivery

Stability-indicating HPLC method for the determination of the stability of oxytocin parenteral solutions prepared in polyolefin bags

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