Evaluation of osmolality and pH of various concentrations of methotrexate, cytarabine, and thiotepa prepared in normal saline, sterile water for injection, and lactated Ringer's solution for intrathecal administration

Abstract

There is limited published literature on the potential impact of diluent and drug concentration on the pH and osmolality of IT chemotherapy preparation. Most cancer centers conventionally prepare IT chemotherapy with 5 mL of preservative diluent normal saline, irrespective of the specific drug or dose used. The conventional practice means that most methotrexate preparations are likely to have comparable pH and osmolality to CSF. In contrast, cytarabine preparations may show significantly higher pH than the CSF, while thiotepa preparations generally have lower osmolality than the CSF.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey

“…No trials have compared the impact of different volumes administered on the CNS distribution. 17 Olmos-Jiménez et al. suggest using a predetermined volume, depending on the patient's age: for infants under a year: 6 ml; in 1 to 2-year toddlers: 8 ml; for 2 to 3-year old toddlers: 10 ml, and; for children over 3 years: 12 ml of normal saline solution as a diluent.…”

Stability of four standardized preparations of methotrexate, cytarabine, and hydrocortisone for intrathecal use

“…However, due to the inherent toxicity of the considered drugs and in an attempt to improve patient's tolerance, in this study it was decided to limit the range of pH at 7-7.5. [4][5][6]…”

“…2 Some of these complications, mainly acute toxicity, have been attributed to the preservatives, volume, osmolarity, and pH of the preparations. 3,4 The use of solutions with pH and osmolarity values close to physiological range of CSF (pH 7.31–7.37, osmolarity 281–306 mOsm/kg) is highly recommended. 5,6 Elliott's B Solution is a buffered salts solution for use as a diluent for the IT administration of antineoplastic drugs; it has been proven that Elliott’s B Solution is comparable to CSF in pH, electrolyte composition, glucose content, and osmolarity 6,7 (Table 1).…”

Cerebrospinal Fluid IL-6, TNF-α and MCP-1 in Children with Acute Lymphoblastic Leukaemia during Chemotherapy

“…Higher levels of pro-infl ammatory agents during protocol M, point to the positive relationship between MTX and neuroinfl ammation. It seems that intrathecal injection of MTX may aff ect alterations in osmolality and induce subclinical meningoencephalitis [ 5 ] . However, infl ammation and oxidative stress also play a role in the anticancer eff ects of therapy and may be an important factor in improving the outcome of ALL therapy.…”