Dosage and usage of histamine phosphate_industrial additives

Background and overview^[1]

Histamine phosphate is mainly used to examine the secretion function of gastric juice to identify the absolute lack of gastric acid in pernicious anemia and the relative lack of gastric cancer. It can also be used to assist in the diagnosis of leprosy. Histamine phosphate is quickly inactivated in the stomach if administered orally. Administered subcutaneously, intramuscularly or intravenously, the effect is rapid and short-lived. Adverse reactions: After overdose, side effects such as flushing of the face, increased heart rate, decreased blood pressure, bronchoconstriction, dyspnea, headache, visual impairment, vomiting and diarrhea may occur, and anaphylactic shock may also occur.

Dosage and usage^[2]

1. Examination of gastric secretion function: In the morning on an empty stomach, inject 0.25 to 0.5 mg of this product subcutaneously, and then test the gastric juice. If there is still no gastric acid secretion, it can be determined as true achlorhydria. Most patients with pernicious anemia and gastric cancer have true achlorhydria and hypochlorhydria.

2. Auxiliary diagnosis of leprosy: use 1:1000 histamine phosphate for intradermal injection and observe the reaction. Normal skin should have a complete triple reaction (that is, an erythema with a diameter of no more than 10mm will appear immediately after injection; Half a minute after the injection, another erythema with a diameter of about 30 to 40 mm appeared around the first erythema; a wheal appeared at the injection site). If the peripheral nerves were damaged, an incomplete triple reaction would occur. A complete triple reaction can rule out leprosy; an incomplete triple reaction can lead to the possibility of leprosy.

3. Desensitization: (1) Prepare the injection to contain 0.1mg, 0.01mg, 0.001mg, 0.0001mg, 0.00001mg per ml. Start with 0.00001mg per ml for subcutaneous injection. 0.5~1ml, then increase the concentration 10 times every day, so as to achieve the purpose of desensitization. (2) Dilute the 1 mg/ml injection 10 times to 0.1 mg/ml, first extract 0.1 ml for subcutaneous injection, and then increase it by 0.1 ml every day until it reaches 1 ml. It can also be desensitized.

Notes^[2]

1. For injections that need to be drawn multiple times during desensitization, bacteriostatic agents should be added.

2. Be alert to the possibility of allergic reactions when using it (if it causes anaphylactic shock, epinephrine can be used to rescue it).

3. Pregnant women, patients with bronchial asthma and patients with a history of allergies are prohibited from taking this product.

Standard^[1]

“Chinese Pharmacopoeia” 1995 edition Part 2, 2000 edition Part 2 and 2005 edition Part 2. In the 1995 edition, the melting point limit was changed to 250~254℃ (ministerial regulation is 250~260℃). There has been no change in the standard since then. In the currently implemented 2005 version of the standard, there are three identifications, among which identification (1) is the determination of the melting point of crystals, and (2) and (3) are chemical reactions. By comparing with the British Pharmacopoeia quotation of PVC resin powder, it was found that identification (1) is not as specific as infrared spectrum identification

Sex. Although there is no control spectrum for histamine phosphate in the infrared spectrum concentration of the Chinese Pharmacopoeia, all histamine phosphate reference substances in the Chinese Pharmacopoeia can be compared with the infrared spectra of the test sample and the control substance. Infrared identification: Take 1 mg of histamine phosphate reference substance, use KBr tableting method, and conduct the test according to infrared spectrophotometry (Chinese Pharmacopoeia Part 2 Appendix IVC): the result is that the infrared spectrum of the sample is consistent with that of the reference substance. The pharmacopoeia does not stipulate histidine, an impurity that may be produced during its production, storage and transportation. This experiment refers to the raw material standards of the British Pharmacopoeia (BP2008 version), and is related to histidine in histamine phosphate injection. Substances are inspected.

1) Reference substance

Reference substance name: histamine phosphate; source: National Inspection Institute; batch number: 150510-9411 histidine; source: National Inspection Institute; batch number: 140624-200104

2) Test solution

Take histamine phosphate and dilute it with water to make a test solution of 50 mg/ml.

3) Measurement method

Control solution a: Take 10 mg of histidine reference substance (equivalent to 12.5 mg of histidine hydrochloride), add water and dilute to 25 ml. Control solution b (system suitability test solution): Mix 1 ml of test solution and 1 ml of control solution a to obtain. Determination method: Take 1 μl of test solution, control solution a, and 2 μl of control solution b respectively, and place them on the same silica gel G plate. Developing agent: concentrated ammonia solution: water: acetonitrile (5:20:75), developing distance: 15cm. Place it in a ventilated place to dry, then use the same method and expand it a second time in the same direction. Place in a ventilated place to dry, spray with ninhydrin test solution, and place at 110°C for color development for 10 minutes. On the chromatogram of the test solution, the color of the spots corresponding to histidine shall not be darker than the spots (1%) shown on the chromatogram of the control solution a. The chromatogram of control solution b should show 2 independent clear spots, otherwise the experiment will be invalid.

On the chromatogram of the test solution, no spots were detected at the spots corresponding to histidine, indicating that no histidine impurities were detected in the test solution; the system suitability solution chromatogram shows 2 separate clear spots, the experiment works. The results show that histamine phosphate and histidine can be separated well, indicating that this method can detect histidine impurities in histamine phosphate injection and is feasible.