Pentaerythritol Trinitrate Research Articles

Molecular dynamics research on effect of doping defects on properties of PETN.

To investigate the effect of doping defects on properties of pentaerythritol tetranitrate (PETN), the "perfect" and doping defective crystal models of PETN containing pentaerythritol (PE), pentaerythritol mononitrate (PEMonoN), pentaerythritol dinitrate (PEDiN), and pentaerythritol trinitrate (PETRIN) were established, respectively. Molecular dynamics (MD) method was applied to perform simulations, and sensitivity, detonation performance, and mechanical properties were calculated and compared. The results indicate that compared with PETN (1 1 0) supercell model, the interaction energy of trigger bond and cohesive energy density of the doped defect models decreased by 2.21~12.43kJmol-1 and 0.0219~0.0421kJcm-3, respectively, indicating that the sensitivity of defective models increases and the safety decreases. The density, detonation velocity, and detonation pressure of the doped defect model decreased by 0.018~0.061gcm-3, 77.833~272.809ms-1, and 0.746~2.544GPa, respectively, and the oxygen balance is declined, indicating that the energy density of PETN decreased and the power decreased. Doped defects also cause the elastic modulus, bulk modulus, and shear modulus of PETN to decrease by 0.75~2.16GPa, 0.44~0.89GPa, and 0.30~0.89GPa, respectively. The ratio of bulk modulus to shear modulus and Cauchy pressure increased by 0.05~0.28GPa and 0.09~1.13GPa, respectively, indicating that the deformation resistance, fracture strength, and hardness of the doped defect model decrease, stiffness decreases, and flexibility and ductility increase.

Explosive detection using a novel dielectric barrier discharge ionisation source for mass spectrometry.

The detection of explosives is of great importance, as is the need for sensitive, reliable techniques that require little or no sample preparation and short run times for high throughput analysis. In this work, a novel ionisation source is presented based on a dielectric barrier discharge (DBD). This not only affects desorption and ionisation but also forms an ionic wind, providing mass transportation of ions towards the mass spectrometer. Furthermore, the design incorporates 2 asymmetric alumina sheets, each containing 3 DBDs, so that a large surface area can be analysed. The DBD operates in ambient air, overcoming the limitation of other plasma-based techniques which typically analyse smaller surface areas and require solvents or gases. A range of explosives across 4 different functional groups was analysed using the DBD with low limits of detection for cyclotrimethylene trinitramine (RDX) (100pg), pentaerythritol trinitrate (PETN) (100pg), hexamethylene triperoxide diamide (HMTD) (1ng), and trinitrotoluene (TNT) (5ng). Detection was achieved without any sample preparation or the addition of reagents to facilitate adduct formation.

UV Resonance Raman Investigation of Pentaerythritol Tetranitrate Solution Photochemistry and Photoproduct Hydrolysis.

Ultraviolet resonance Raman spectroscopy (UVRR) is being developed for standoff trace explosives detection. To accomplish this, it is important to develop a deep understanding of the accompanying UV excited photochemistry of explosives, as well as the impact of reactions on the resulting photoproducts. In the work here we used 229 nm excited UVRR spectroscopy to monitor the photochemistry of pentaerythritol tetranitrate (PETN) in acetonitrile. We find that solutions of PETN in CD3CN photodegrade with a quantum yield of 0.08 ± 0.02, as measured by high performance liquid chromatography (HPLC). The initial step in the 229 nm UV photolysis of PETN in CD3CN is cleavage of an O-NO2 bond to form NO2. The accompanying photoproduct is pentaerythritol trinitrate (PETriN), (CH2ONO2)3CCH2OH formed by photolysis of a single O-NO2. The resulting UVRR spectra show a dominant photoproduct band at ∼1308 cm-1, which derives from the symmetric stretch of dissolved NO2. This photoproduct NO2 is hydrolyzed by trace amounts of water, which downshifts this 1308 cm-1 NO2 Raman band due to the formation of molecular HNO3. The dissociation of HNO3 to NO3- in the presence of additional water results in an intense NO3- symmetric stretching UVRR band at 1044 cm-1.

Identification of peptide sequences that selectively bind to pentaerythritol trinitrate hemisuccinate‐a surrogate of PETN, via phage display technology

The present research investigates the identification of amino acid sequences that selectively bind to a pentaerythritol tetranitrate (PETN) explosive surrogate. Through the use of a phage display technique and enzyme-linked immunosorbent assays (ELISA), a peptide library was tested against pentaerythritol trinitrate hemisuccinate (PETNH), a surrogate of PETN, to screen for those with amino acids having affinity toward the explosive. The results suggest that the library contains peptides selective to PETNH. Following three rounds of panning, clones were picked and tested for specificity toward PETNH. ELISA results from these samples show that each phage clone has some level of selectivity for binding to PETNH. The peptides from these clones have been sequenced and shown to contain certain common amino acid segments among them. This work represents a technological platform for identifying amino-acid sequences selective toward any bio-chem analyte of interest.

Pentaerythritol Trinitrate Substituted s-Tetrazine and s-Triazine

The synthesis of pentaerythritol trinitrate persubstituted 1,2,4,5-tetrazine and 1,3,5-triazine is reported. These materials were characterized with respect to their chemical and energetic materials properties. X-ray crystallographic analyses were also performed. The UV/Vis, Raman, and cyclic voltammetry data were collected and are reported.

Photoactive high explosives: linear and nonlinear photochemistry of petrin tetrazine chloride.

Pentaerythritol tetranitrate (PETN), a high explosive, initiates with traditional shock and thermal mechanisms. In this study, the tetrazine-substituted derivative of PETN, pentaerythritol trinitrate chlorotetrazine (PetrinTzCl), is being investigated for a photochemical initiation mechanism that could allow control over the chemistry contributing to decomposition leading to initiation. PetrinTzCl exhibits a photochemical quantum yield (QYPC) at 532 nm not evident with PETN. Using static spectroscopic methods, we observe energy absorption on the tetrazine (Tz) ring that results in photodissociation yielding N2, Cl-CN, and Petrin-CN as the major photoproducts. The QYPC was enhanced with increasing irradiation intensity. Experiment and theoretical calculations imply this excitation mechanism follows sequential photon absorption. Dynamic simulations demonstrate that the relaxation mechanism leading to the observed photochemistry in PetrinTzCl is due to vibrational excitation during internal conversion. PetrinTzCl's single photon stability and intensity dependence suggest this material could be stable in ambient lighting, yet possible to initiate with short-pulsed lasers.

Accurate quantitation of pentaerythritol tetranitrate and its degradation products using liquid chromatography–atmospheric pressure chemical ionization–mass spectrometry

After an explosion of pentaerythritol tetranitrate (PETN), its degradation products pentaerythritol trinitrate (PETriN), dinitrate (PEDiN) and mononitrate (PEMN) were detected using liquid chromatography–atmospheric-pressure chemical-ionization–mass spectrometry (LC–APCI–MS). Discrimination between post-explosion and naturally degraded PETN could be achieved based on the relative amounts of the degradation products. This information can be used as evidence when investigating a possible relationship between a suspect and a post-explosion crime scene. The present work focuses on accurate quantitation of PETN and its degradation products, using PETriN, PEDiN and PEMN standards specifically synthesized for this purpose. With the use of these standards, the ionization behavior of these compounds was studied, and a quantitative method was developed. Quantitation of PETN and trace levels of its degradation products was shown to be possible with accuracy between 85.7% and 103.7% and a precision ranging from 1.3% to 11.5%. The custom-made standards resulted in a more robust and reliable method to discriminate between post-explosion and naturally-degraded PETN.

Pentaerythritol tetranitrate (PETN) profiling in post-explosion residues to constitute evidence of crime-scene presence

Pentaerythritol tetranitrate (PETN) and its degradation products are analyzed to discriminate between residues originating from PETN explosions and residues obtained under other circumstances, such as natural degradation on textile, or after handling intact PETN. The degradation products observed in post-explosion samples were identified using liquid chromatography–mass spectrometry as the less-nitrated analogues of PETN: pentaerythritol trinitrate (PETriN), pentaerythritol dinitrate (PEDiN) and pentaerythritol mononitrate (PEMN). Significant levels of these degradation products were observed in post-explosion samples, whereas only very low levels were detected in a variety of intact PETN samples and naturally degraded PETN. No significant degradation was observed after 12 weeks of storage at room temperature and the influence of high relative humidity (90%) was found to be small. Natural degradation was accelerated by storage of small amounts of PETN on different types of textile, resembling the clothing of a suspect, at elevated temperature (333K). This resulted in significant levels of PETN degradation products, but the relative amounts remained much lower than in post-explosion PETN. For PETriN the peak area relative to PETN was 0.014 (SD=0.0051) and 0.39 (SD=0.19) respectively. Based on the peak areas of PETriN, PEDiN and PEMN relative to PETN, it was possible to fully distinguish the post-explosion profiles from the profiles obtained from intact PETN or after (accelerated) natural degradation.Although more data are required to accurately assess the strength of the evidence, this work illustrates that PETN profiling may yield valuable evidence when investigating a possible link between a suspect and post-explosion PETN found on a crime scene. Due to the substantial variation in the degradation pattern between explosion experiments and even between sampling positions in one experiment, the method is not able to distinguish different PETN explosion events.

Degradation of Pentaerythritol Tetranitrate (PETN) by Granular Iron

Pentaerythritol tetranitrate (PETN), a nitrate ester, is used primarily as an explosive. It is of environmental concern, posing a threat to aquatic organisms with an estimated EC50 five times greater than that of RDX. This study evaluated the kinetics and products of PETN degradation in the presence of granular iron. PETN transformation in columns containing 100% granular iron and 30% iron mixed with 70% silica sand followed pseudo first-order kinetics, with average half-lives of 0.26 and 1.58 min, respectively. The reduction pathway was proposed to be sequential denitration, in which PETN was stepwise reduced to pentaerythritol with the formation of pentaerythritol trinitrate and pentaerythritol dinitrate as intermediates. The intermediate of pentaerythritol mononitrate was not detected; however, the nearly 100% nitrogen mass recovery supported complete denitration. Nitrite was released in each denitration step and was subsequently reduced to ammonium by iron. Nitrate was not detected during the experiment suggesting that hydrolysis was not involved in PETN degradation. Batch experiments showed that when solid-phase PETN is present, dissolution is the rate-limiting factorfor PETN mass removal. Using 50% methanol as a cosolvent PETN solubility was enhanced and thus the removal efficiency was improved. The results demonstrate excellent potential of using iron to remediate PETN-contaminated water.

Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress

Reduced levels and impaired function of endothelial progenitor cells (EPCs) foster development and progression of atherosclerotic lesions. Endothelial nitric oxide synthase (eNOS)-derived NO regulates EPC mobilization and function. Organic nitrates release NO, and therefore may favorably affect EPC biology. We compared the effects of 2 different nitrates on circulating EPC numbers and function. Treatment of rats with pentaerythritol-trinitrate (PETriN) or isosorbide dinitrate (ISDN) increased circulating EPC levels. EPC from ISDN- but not PETriN-treated animals displayed impaired migratory capacity and increased reactive oxygen species formation in EPCs. In vitro treatment with ISDN reduced migration and incorporation of human EPCs into vascular structures on matrigel, whereas PETriN improved EPC function. ISDN, but not PETriN, increased NADPH oxidase-mediated oxidative stress in cultured human EPCs. Addition of polyethylene-glycolated superoxide dismutase or diphenyliodonium normalized both ISDN-induced superoxide anion production and impaired migratory capacity of EPCs. Long-acting nitrates increase levels of circulating EPCs, but differ in their effects on EPC function dependent on the induction of intracellular oxidative stress. Organic nitrates that improve EPC function may confer long-term cardiovascular protection based on their beneficial effects on EPC biology.

Oxidative stress and mitochondrial aldehyde dehydrogenase activity: a comparison of pentaerythritol tetranitrate with other organic nitrates.

Mitochondrial aldehyde dehydrogenase (ALDH-2) was recently identified to be essential for the bioactivation of glyceryl trinitrate (GTN). Here we assessed whether other organic nitrates are bioactivated by a similar mechanism. The ALDH-2 inhibitor benomyl reduced the vasodilator potency, but not the efficacy, of GTN, pentaerythritol tetranitrate (PETN), and pentaerythritol trinitrate in phenylephrine-constricted rat aorta, whereas vasodilator responses to isosorbide dinitrate, isosorbide-5-mononitrate, pentaerythritol dinitrate, pentaerythritol mononitrate, and the endothelium-dependent vasodilator acetylcholine were not affected. Likewise, benomyl decreased GTN- and PETN-elicited phosphorylation of the cGMP-activated protein kinase substrate vasodilator-stimulated phosphoprotein (VASP) but not that elicited by other nitrates. The vasodilator potency of organic nitrates correlated with their potency to inhibit ALDH-2 dehydrogenase activity in mitochondria from rat heart and increase mitochondrial superoxide formation, as detected by chemiluminescence. In contrast, mitochondrial ALDH-2 esterase activity was not affected by PETN and its metabolites, whereas it was inhibited by benomyl, GTN applied in vitro and in vivo, and some sulfhydryl oxidants. The bioactivation-related metabolism of GTN to glyceryl-1,2-dinitrate by isolated RAW macrophages was reduced by the ALDH-2 inhibitors benomyl and daidzin, as well as by GTN at concentrations >1 microM. We conclude that mitochondrial ALDH-2, specifically its esterase activity, is required for the bioactivation of the organic nitrates with high vasodilator potency, such as GTN and PETN, but not for the less potent nitrates. It is interesting that ALDH-2 esterase activity was inhibited by GTN only, not by the other nitrates tested. This difference might explain why GTN elicits mitochondrial superoxide formation and nitrate tolerance with the highest potency.

Effects of nonintermittent treatment of rabbits with pentaerythritol tetranitrate on vascular reactivity and superoxide production

Pentaerythritol tetranitrate is an organic nitrate ester that undergoes metabolization to pentaerythritol, pentaerythritol trinitrate, pentaerythritol dinitrate and pentaerythritol mononitrate. Recent data suggested that pentaerythritol tetranitrate is endowed with vasoprotective activities in experimental atherosclerosis. This study was undertaken to gain insight into the underlying mechanism. The basic mechanism of action of all pentaerythritol nitrates was evaluated by measuring liberation of nitric oxide (NO), stimulation of human soluble guanylate cyclase and vasorelaxation in rabbit aorta. A subsequent in vivo study in New Zealand White rabbits was performed to investigate the effects of a 4 months lasting nonintermittent oral treatment with 6 mg pentaerythritol tetranitrate kg −1 day −1 on vascular superoxide production, endothelium dependent vasorelaxation and vasorelaxation to pentaerythritol tetranitrate itself. The formation rates of NO from the pentaerythritol nitrates (100 μM, n=5) in presence of 5 mM cystein were (in nM min −1): 62.1±3.2 (pentaerythritol tetranitrate), 21.3±0.9 (pentaerythritol trinitrate), 6.4±0.6 (pentaerythritol dinitrate) and 3.2±0.4 (pentaerythritol mononitrate). Similarly, the pD 2 values (−log M) for half-maximal activation of soluble guanylate cyclase decreased from pentaerythritol tetranitrate (3.391±0.09, n=4) to pentaerythritol mononitrate (2.655±0.04, n=3) as did the p D 2 values (in −log M) for half-maximal relaxation of rabbit aortic rings ( n=7) from pentaerythritol tetranitrate (8.3±0.17) to pentaerythritol mononitrate (5.0±0.11). Significant correlations were found between the NO formation rates and the p D 2 values for enzyme stimulation ( r=0.98, P=0.002) and vasorelaxation ( r=0.90, P=0.049) suggesting that these effects of the pentaerythritol nitrates were mediated by NO. The results of the in vivo study showed that aging induces a significant increase of aortic superoxide production (median values, n=10) from 2.45 nM mg −1 min −1 (age 7 months) to 3.39 nM mg −1 min −1 (age 11 months, P<0.01) that was prevented by concurrent treatment with pentaerythritol tetranitrate (2.76 nM mg −1 min −1). In vitro vasorelaxation to pentaerythritol tetranitrate was identical in all groups indicating absence of nitrate tolerance. Endothelium-dependent vasorelaxation was also identical in all groups. These data suggest that oral treatment with pentaerythritol tetranitrate reduces vascular oxidant stress by an NO-dependent pathway, which may contribute to the vasoprotective activity of pentaerythritol tetranitrate in experimental atherosclerosis.

A common enzyme may be responsible for the conversion of organic nitrates to nitric oxide in vascular microsomes

We compared the nitric oxide (NO)-generating behavior of nitroglycerin (NTG), pentaerythritol trinitrate (PEtriN) and isosorbide dinitrate (ISDN), in the microsomal preparation of bovine coronary artery smooth muscle cells. The comparative NO generating activities among these nitrates were consistent with their relative reported vasodilating activities. Consistent with our previous observations with NTG, 400 μM bromosulfophthalein did not affect NO generation from PEtriN and ISDN in vascular microsomes while 400 μM 1-chloro-2,4-dinitrobenzene completely inhibited NO generation from these nitrates. Gel filtration chromatography with solubilized microsomes of bovine aortic smooth muscle cells showed the primary activity of NO generation from all three nitrates to be eluted at about 200 kD, consistent with that found with solubilized microsomes from the bovine coronary artery microsomes. These results suggest that organic nitrates may be converted to NO by one common enzyme in vascular microsomes.

Metabolism of pentaerythritol trinitrate.

The absorption, excretion, and biotransformation of 14C-labeled pentaerythritol (PE) trinitrate was studied in man. The administration of a single sublingual dose was followed by rapid absorption and extensive biotransformation. Six drug metabolites were identified. Final excretion of the drug and its metabolites was almost totally through the kidney. Low levels of unchanged drug were present in plasma and urine. PE mononitrate was the major drug metabolite in plasma and urine. Glucuronides of PE trinitrate, dinitrate, and mononitrate were identified for the first time in man. PE trinitrate glucuronide appeared in plasma rapidly and about 8% of the dose was excreted in urine. Reversible and irreversible pathways are proposed for the formation of the metabolites. The reconversion of PE trinitrate glucuronide to PE trinitrate is postulated to explain the duration of drug activity and excretion.

Pentaerythritol trinitrate and glyceryl trinitrate on intramyocardial oxygenation and perfusion in the dog. Krogh analysis of transmural metabolism.

1. The effect of intravenous pentaerythritol trinitrate and glyceryl trinitrate on left ventricular subepicardial (epi) and subendocardial (endo) PO2 and perfusion were compared in anaesthetized open-chest mongrel dogs. Tissue PO2 was determined simultaneously at a depth of 3 mm (epicardial) and 9 mm (endocardial) with small platinum electrodes by polarography. In a separate series of dogs tissue perfusion of those regions was measured by hydrogen (H2) clearance using similar electrodes. 2. Both nitrates increased endocardial PO2 while epicardial PO2 was not altered. Perfusion was determined at the point of the maximal rise in endocardial PO2 (4-7 min after injection of either nitrate). At that period average coronary artery inflow and epicardial perfusion were decreased but endocardial perfusion was not significantly altered. 3. Using the data on PO2, hydrogen clearance and intercapillary distance, the effect of the nitrates on transmural metabolism (oxygen consumption) was estimated by Krogh analysis. Basal endocardial metabolism was 20-30% higher than epicardial metabolism. The nitrates reduced metabolism in each region. The absolute decrease in oxygen consumption was greater in the endocardium. 4. The results show that both pentaerythritol trinitrate and glyceryl trinitrate improve endocardial oxygenation by producing a more favourable balance between perfusion and oxygen requirements in that region.

Pentaerythritol trinitrate and glyceryl trinitrate on myocardial oxygen consumption and haemodynamics in the dog.

1. The effects of pentaerythritol trinitrate (pentrinitrol) and glyceryl trinitrate on myocardial oxygen consumption and myocardial and systemic haemodynamics were studied in anaesthetized open-chest dogs. An in vivo oximeter in the coronary sinus permitted continuous determination of arteriovenous oxygen difference and myocardial oxygen consumption. All parameters were determined simultaneously at various intervals after drug administration. 2. Myocardial oxygen consumption was diminished by both nitrates for more than 16 min. Changes in arteriovenous oxygen difference and coronary sinus oxygen content were variable between drugs. Following an initial transient increase, coronary blood flow was reduced by both nitrates. Aortic blood pressure, aortic blood flow, left ventricular end-diastolic pressure and left ventricular dP/dt were also reduced. Heart rate and contractile force were not appreciably altered by either nitrate. 3. The decrease in myocardial oxygen consumption appears to be associated with the haemodynamic profile of these drugs. Both nitrates produced comparable reductions in preload (left ventricular end-diastolic pressure) and afterload (aortic pressure) as well as dP/dt.

Comparative vasodilator effects of nitroglycerin, pentaerythritol trinitrate and biometabolites, and other organic nitrates

Previous studies in man have shown pentaerythritol (PE) trinitrate, given either sublingually or orally, produces a prolonged hypotensive effect. The coronary vasodilator and systemic vasoddepressor activities of PE trinitrate and its metabolites, PE dinitrate, PE mononitrate and PE, were evaluated in dogs to determine whether the metabolites were active and contributory. Coronary vasodilator activity was estimated with a flow transducer placed on the left anterior descending artery, and reduction of arterial pressure was determined directly via the femoral artery. Quantitative comparisons were made from dose—response curves established for nitroglycerin (NG), PE nitrates, and other common organic nitrates after intrajugular administration. Increase of coronary blood flow and reduction of arterial pressure were proportionally related, and the proportionality was the same for all drugs. Relative to NG, the potency of PE trinitrate was about 20%, erythrityl tetranitrate 12%, and isosorbide dinitrate 3.5%. The ratios of vasodilator activity of PE trinitrate and its metabolites were: PE trinitrate 100; PE dinitrate 1.5; PE mononitrate 0.5; and PE 0. Tachyphylaxis was observed after close-order injections of NG or PE trinitrate. In addition, there was cross tolerance between NG and PE trinitrate and also between PE trinitrate and its less active metabolites.

Intracoronary nitroglycerin, pentaerythritol trinitrate and dipyridamole on intramyocardial oxygen tension

The effects of intracoronary injection of nitroglycerin, pentaerythritol trinitrate and dipyridamole on subepicardial (epi) and subendocardial (endo) oxygen tension were compared in anaesthetized open chest dogs. The P O 2 was determined simultaneously at a depth of 3 mm (epi) and 9 mm (endo) below the surface of the left ventricle with small platinum electrodes by a polarographic method. The two nitrates produced a selective increase in endo P O 2 , no change in epi P O 2 and a transient increase in coronary blood flow. In some cases, endo P O 2 increased in the absence of a significant rise in blood flow. Dipyridamole consistently caused a prolonged increase in coronary flow; epi P O 2 increased slightly and endo P O 2 decreased in some of the animals. Using data for nitroglycerin on P O 2 , regional blood flow and intercapillary distance, the changes in metabolism were predicted on the basis of the Krogh analysis. Metabolism was reduced in both epi and endo; P O 2 and blood flow were increased in endo and decreased in epi, and intercapillary distances were unchanged. It is concluded that the nitrates increase endo P O 2 of the left ventricle by a decrease in metabolism and redistribution of blood flow to endo from epi.

Biliary excretion and biotransformation of pentaerythritol trinitrate in rats

A study was made of the biliary excretion of 14C-pentaerythritol trinitrate in the rat to elucidate the possible role of enterohepatic circulation in the prolonged action of the drug. The biliary drug excretion consisted entirely of metabolites which were previously unknown, namely, the glucuronides of pentaerythritol mononitrate, dinitrate and trinitrate. Drug radioactivity entered the bile faster after intravenous than after oral dosing. This difference (51% vs. 30% of the dose in 4 hr) was entirely due to pentaerythritol dinitrate glucuronide; the pentaerythritol trinitrate glucuronide level was approximately the same (9.5% of the dose in 4 hr). Enterohepatic circulation was indicated by the observation that 2.5 times more drug radioactivity was excreted into the urine by intact rats than by biliary cannulated rats. A comparison of the biliary and urinary excretion products of pentaerythritol trinitrate suggests that the enterohepatic circulation provides the opportunity for gastrointestinal resorption and recirculation of the free drug.

The pharmacodynamics and biotransformation of pentaerythritol trinitrate in man.

Pentaerythritol trinitrate (PE‐trinitrate), a metabolite in man of pentaerythritol tetranitrate (PETN), has been found to possess considerably greater vasodilator activity than its parent drug. Pharmacokinetics and metabolism of PE‐trinitrate were studied after single sublingual and oral doses of 14C‐PE‐trinitrate given in clinical dosage form. Drug absorption rate constants obtained from blood concentrations of drug radioactivity showed that absorption was rapid with both modes of administration. Metabolism and elimination after both dosage modes were nearly identical. The drug was not found in urine or in blood except within a few minutes of administration. Urinary elimination of metabolites accounted for 92 per cent of the dose, with less than 2 per cent recovered in fecal excretion as pentaerythritol (PE). The principal urinary metabolites were PE (30 per cent) and PE‐mononitrate (69 per cent). Excretion of these metabolites was first order with half‐times of elimination of 10.5 and 7.3 hours, respectively. From a comparison of the pharmacokinetics and biotransformation of PE‐trinitrate with those previously observed for PETN in similar experimental conditions, it is suggested that the rates of absorption and intracellular accumulation at tissue sites of action are primary determinants of the pharmacological activity and relative potencies of the organic nitrates.