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Background: Although several dexamethasone phosphate preparations are commercially available and frequently administered with octreotide acetate, their compatibility remains unknown. Aim: We investigated the effect of pH and sodium bisulphate on the stability of octreotide acetate. Measurement design: Octreotide acetate percentage was measured 3 and 10 days after it was mixed with 2 dexamethasone phosphate preparations containing different concentrations of sodium bisulphate as an additive, and in one that did not contain sodium bisulphate. Solutions were also analysed after they were prepared using phosphate buffer to achieve pH values of 4.0, 7.0, and 9.0. The initial octreotide acetate concentration was 41.7 g/mL. High−performance liquid chromatography was used for measurement. Results: The octreotide acetate percentage in the mixture with dexamethasone phosphate without sodium bisulphate was maintained at 95% for up to 10 days. However, mixing octreotide acetate with the other 2 agents resulted in a significant decrease to 85%. The octreotide acetate percentage was ＜90% after sodium bisulphate−containing solution was stored at room temperature under light−protected conditions for 3 days. The percentage of octreotide acetate in the pH 7.0 solution was ＜90% three days after preparation; however, in the pH 4.0 solution, it was maintained at 95% for up to 10 days. Conclusions: Our results suggest that octreotide acetate is hydrolysed in the presence of sodium bisulphate, leading to a decrease in the percentage of octreotide acetate in the solution, which can be avoided using sodium bisulphate−free dexamethasone phosphate preparations. Palliat Care Res 2013; 8(2): 177−83

PurposeSodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate.MethodsAlthough morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography.ResultsOctreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations.ConclusionsThese results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

Introduction ; Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease that can be subdivided according to primary recurrent genetic abnormalities that are strongly associated with characteristic biological and clinical features. In approximately two-thirds of pediatric patients with BCP-ALL, well-characterized genetic abnormalities can be detected by standard genetic analyses. In the remaining BCP-ALL patients, major pathogenic or driver cytogenetic abnormalities have yet to be clarified and they are called B-others. Recent studies using advanced analytical approaches have stratified a variety of subgroups harboring novel genetic abnormalities. For example, Ph-like ALL, iAMP21, deletion of ERG and rearrangements of ZNF384 and MEF2D have been identified in B-others. However, a certain portion of B-others still remains as genetically unclassified. Patients and Methods; 291 children with de novo BCP-ALL were enrolled on Tokyo Children Cancer Study Group (TCCSG) ALL L0416 and L0616 trials (between 2004-2007). Conventional genetic abnormalities, including BCR-ABL1, MLL-AF4, MLL-AF9, TCF3-PBX1, ETV6-RUNX1, hyperdiploidy and hypodiploidy were detected in 16 (5.5%), 3 (1.0%), 2 (0.7%), 18 (6.2%), 54 (18.5%), 65 (22.3%) and 3 (1.0%) cases by G-banding, fluorescent in situ hybridization and molecular analyses. 131 cases (44.9%) were classified B-others. We studied 121 (93.1%) out of 131 B-others ALL of the L0416/L0616 cohort. We performed whole transcriptome sequencing (WTS) of 35 pediatric B-others cases. For the confirmation and screening of the fusion transcripts we performed RT-PCR in a total of 121 B-others cases. Alterations of ERG and iAMP21 were examined by Multiplex Ligation-dependent Probe Amplification (MLPA) kit P327. We also analyzed the known genetic mutations or copy number alterations associated with these patients using the data from WTS and MLPA kit P335 and P200. Results; A total of 47 candidate in-frame gene rearrangements were identified in 29/35 (82.8%) B-others samples. The fusion genes including ZNF384 (n=12, 4.1%) or MEF2D (n=6, 2.1%) were frequently found in this cohort. All of patients with ZNF384-related fusion genes were found to have a weak or negative expression of CD10. In addition, 7 and 17 patients out of 22 patients with ZNF384-related fusion genes exhibited more than 20% expression of CD13 and CD33. We identified 6 recurrently mutated genes, including NRAS, KRAS, PTPN11, EZH2, MLL2 and ASH1L. Especially, activating mutations in RAS signaling pathway genes, including NRAS, KRAS and PTPN11 were detected in 4 out of 10 ZNF384-translocated patients. Mutations in B-cell developmental genes such as PAX5, BTG1 and IKZF1 were not detected at all in DNA samples with ZNF384-related fusion genes. We identified a total of 6 (1.8%) patients with the fusion genes related with Ph-like ALL, including IGHM-CRLF2, P2RY8-CRLF2, IGH@-EPOR and PAX5-JAK2. Three of 6 patients with Ph-like ALL related fusion gene relapsed and two patients died. We identified iAMP21 in 6 (2.1%) patients and deletion of ERG in 7 (2.4%). One of 6 patients with iAMP21 and 3 of 8 patients with ERG deletion had IKZF1 deletion. No mutations of CRLF2 and JAK2 were identified in patients with iAMP21 and ERG deletion. Among 6 patients with iAMP21, three patients relapsed, and two patients died. No patients with ERG deletion relapsed or died. Conclusions; WTS analysis unmasked a complexity of gene rearrangements in pediatric BCP-ALL without conventional genetic abnormalities. In this study, 10.6% of genetic alterations were revealed in Japanese pediatric B-others cohort. Apart from increasing our understanding of the pathogenesis of pediatric BCP-ALL, this may help improve risk stratification and eventually increase the therapeutic option. Disclosures No relevant conflicts of interest to declare.