Injection buffer capacity

When calcium carbonate goes into solution, it releases basic carbonate ions (COf ), which react with hydrogen ions to form carbon dioxide (which will normally remain in solution at deep-well-injection pressures) and water. Removal of hydrogen ions raises the pH of the solution. However, aqueous carbon dioxide serves to buffer the solution (i.e., re-forms carbonic acid in reaction with water to add H+ ions to solution). Consequently, the buffering capacity of the solution must be exceeded before complete neutralization will take place. Nitric acid can react with certain alcohols and ketones under increased pressure to increase the pH of the solution, and this reaction was proposed by Goolsby41 to explain the lower-than-expected level of calcium ions in backflowed waste at the Monsanto waste injection facility in Florida. 

The onset of local anesthesia can be accelerated by the addition of sodium bicarbonate (1-2 mL) to the local anesthetic solution. This maximizes the amount of drug in the more lipid-soluble (unionized) form. Repeated injections of local anesthetics can result in loss of effectiveness (ie, tachyphylaxis) due to extracellular acidosis. Local anesthetics are commonly marketed as hydrochloride salts (pH 4.0-6.0) to maximize aqueous solubility. After injection, the salts are buffered in the tissue to physiologic pH, thereby providing sufficient free base concentration for diffusion through the axonal membrane. However, repeated injections of the local anesthetic can deplete the buffering capacity of the local tissues. The ensuing acidosis increases the extracellular cationic form, which diffuses poorly and results in tachyphylaxis. Tachyphylaxis to local anesthetics is common in areas with a limited buffer capacity (eg, the cerebrospinal fluid). 

Furosemide injection may be administered by slow IV injection or by intermittent or continuous IV infusion at a rate not exceeding 4 mL/min. Therefore, the question arises whether photoprotection of the drug reservoir is necessary during parenteral administration. Furosemide injection contains the sodium salt of furosemide formed in situ by the addition of sodium hydroxide during the manufacturing process. The injection solution has a pH of 8 to 9.3. In use, it can be mixed with weakly alkaline and neutral infusion solutions (e.g., 0.9% sodium chloride or Ringer s solution) or with some weakly acidic solutions having a low buffer capacity (e.g., dextrose 5% in water). 

Despite these considerations, the first approach in method development for ESl-MS is the formation of preformed ions in solution, i.e., protonation of basic analytes or deprotonation of acidic analytes. Thus, for basic analytes, mixtures of ammonium salts and volatile acids like formic and acetic acid are applied. Alternatively, formic or acetic acid may be added to the mobile phase, just to set a low pH for the generation of preformed ions in solution. The latter approach is successful if sufficient hydrophobic interaction between preformed aiialyte ions and the reversed-phase material remains. The concentration of buffer is kept as low as possible, i.e., at or below 10 nunol/1 in ESl-MS. The buffer concentration is obviously determined by the buffer capacity needed to achieve stable pH conditions upon repetitive injection of the samples. Constantopoulos et al. [99] derived an equilibrium partitioning model to predict the effect of the salt concentration on the analyte response in ESI. If the salt concentration is below 10 moFl, the analyte response is proportional to its concentration. The response is found to decrease with increasing salt concentration. 

Ionic strength is particularly important for ion-exchange HPLC methods. Other factors affecting mobile phase, such as pH, must also be controlled. If the injected sample overwhelms the buffering capacity, then retention behavior will be affected if it is dependent on pH. 

Concentrates or powders for injections or infusions may be diluted, dissolved, or suspended ex tempore in several different media prior to administration. The most common solutions for this purpose are listed in Table 14.3. These are sterile, isotonic, aqueous solutions, but differ with respect to pH, ionic strength, buffer capacity, and chemical composition. As described in Section 14.2, these physicochemical properties may be highly important for the photochemical stability of a dissolved compound choice of medium can be critical and photochemical behavior can change dramatically in different media. 

B. A. Woods, J. RMi5ka, G. D. Christian, and R. J. Charlson, Measurement of pH in Solutions of Low Buffering Capacity and Low Ionic Strength by Optosensing Flow Injection Analysis. Anal. Chem., 58 (1986) 2496. 

From a practical point of view, the octanol-water partition coefficient of benzoic acid is 74 (log = 1.87), its acid dissociation constant is 6.3 x 10 (pAia = 4.2), and its dimerization constant, k2, is about 0.04. At physiological pH of 7.4, benzoic acid is exclusively in the benzoate anion form. Eq. 4 gives a Dq/w value of 0.05 whatever be the benzoic acid concentration injected (the buffer capacity is assumed to be high). When 1 Mbenzoic acid is injected in a pH 1 buffered aqueous phase, the measured Dq/w value will be 77. A 0.1 M injection at pH 1 would produce a Dq/w value of 74.3. In all cases, the Pq/w coefficient is 74. The peak position of benzoic acid in the CCC chromatogram critically depends on the aqueous phase pH and marginally on the injected concentration. 

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